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Complex systems are inherently multilevel and multiscale systems. The infectious disease system is considered a complex system resulting from the interaction between three sub-systems (host, pathogen, and environment) organized into a hierarchical structure, ranging from the cellular to the macro-ecosystem level, with multiscales. Therefore, to describe infectious disease phenomena that change through time and space and at different scales, we built a model framework where infectious disease must be considered the set of biological responses of human hosts to pathogens, with biological pathways shared with other pathologies in an ecological interaction context. In this paper, we aimed to design a framework for building a disease model for COVID-19 based on current literature evidence. The model was set up by identifying the molecular pathophysiology related to the COVID-19 phenotypes, collecting the mechanistic knowledge scattered across scientific literature and bioinformatic databases, and integrating it using a logical/conceptual model systems biology. The model framework building process began from the results of a domain-based literature review regarding a multiomics approach to COVID-19. This evidence allowed us to define a framework of COVID-19 conceptual model and to report all concepts in a multilevel and multiscale structure. The same interdisciplinary working groups that carried out the scoping review were involved. The conclusive result is a conceptual method to design multiscale models of infectious diseases. The methodology, applied in this paper, is a set of partially ordered research and development activities that result in a COVID-19 multiscale model.
Francesco Messina; Chiara Montaldo; Isabella Abbate; Manuela Antonioli; Veronica Bordoni; Giulia Matusali; Alessandra Sacchi; Emanuela Giombini; Gian Fimia; Mauro Piacentini; Maria Capobianchi; Francesco Lauria; Giuseppe Ippolito; on behalf of COVID-19 Scoping Review Working Group. Rationale and Criteria for a COVID-19 Model Framework. Viruses 2021, 13, 1309 .
AMA StyleFrancesco Messina, Chiara Montaldo, Isabella Abbate, Manuela Antonioli, Veronica Bordoni, Giulia Matusali, Alessandra Sacchi, Emanuela Giombini, Gian Fimia, Mauro Piacentini, Maria Capobianchi, Francesco Lauria, Giuseppe Ippolito, on behalf of COVID-19 Scoping Review Working Group. Rationale and Criteria for a COVID-19 Model Framework. Viruses. 2021; 13 (7):1309.
Chicago/Turabian StyleFrancesco Messina; Chiara Montaldo; Isabella Abbate; Manuela Antonioli; Veronica Bordoni; Giulia Matusali; Alessandra Sacchi; Emanuela Giombini; Gian Fimia; Mauro Piacentini; Maria Capobianchi; Francesco Lauria; Giuseppe Ippolito; on behalf of COVID-19 Scoping Review Working Group. 2021. "Rationale and Criteria for a COVID-19 Model Framework." Viruses 13, no. 7: 1309.
Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.
Saeid Najafi Fard; Linda Petrone; Elisa Petruccioli; Tonino Alonzi; Giulia Matusali; Francesca Colavita; Concetta Castilletti; Maria Rosaria Capobianchi; Delia Goletti. In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses. BioMed Research International 2021, 2021, 1 -21.
AMA StyleSaeid Najafi Fard, Linda Petrone, Elisa Petruccioli, Tonino Alonzi, Giulia Matusali, Francesca Colavita, Concetta Castilletti, Maria Rosaria Capobianchi, Delia Goletti. In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses. BioMed Research International. 2021; 2021 ():1-21.
Chicago/Turabian StyleSaeid Najafi Fard; Linda Petrone; Elisa Petruccioli; Tonino Alonzi; Giulia Matusali; Francesca Colavita; Concetta Castilletti; Maria Rosaria Capobianchi; Delia Goletti. 2021. "In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses." BioMed Research International 2021, no. : 1-21.
Vaccination is the main public health measure to reduce SARS-CoV-2 transmission and hospitalization, and a massive worldwide scientific effort resulted in the rapid development of effective vaccines. This work aimed to define the dynamics of humoral and cell-mediated immune response in a cohort of health care workers (HCWs) who received a two-dose BNT162b2-mRNA vaccination. The serological response was evaluated by quantifying the anti-RBD and neutralizing antibodies. The cell-mediated response was performed by a whole blood test quantifying Th1 cytokines (IFN-γ, TNF-α, IL-2), produced in response to spike peptides. The BNT162b2-mRNA vaccine induced both humoral and cell-mediated immune responses against spike peptides in virtually all HCWs without previous SARS-CoV-2 infection, with a moderate inverse relation with age in the anti-RBD response. Spike-specific T cells produced several Th1 cytokines (IFN-γ, TNF-α, and IL-2), which correlated with the specific-serological response. Overall, our study describes the ability of the BNT162b2 mRNA vaccine to elicit a coordinated neutralizing humoral and spike-specific T cell response in HCWs. Assessing the dynamics of these parameters by an easy immune monitoring protocol can allow for the evaluation of the persistence of the vaccine response in order to define the optimal vaccination strategy.
Chiara Agrati; Concetta Castilletti; Delia Goletti; Silvia Meschi; Alessandra Sacchi; Giulia Matusali; Veronica Bordoni; Linda Petrone; Daniele Lapa; Stefania Notari; Valentina Vanini; Francesca Colavita; Alessandra Aiello; Alessandro Agresta; Chiara Farroni; Germana Grassi; Sara Leone; Francesco Vaia; Maria Capobianchi; Giuseppe Ippolito; Vincenzo Puro; on behalf of the INMI COVID-190 Vaccine Study Group. Coordinate Induction of Humoral and Spike Specific T-Cell Response in a Cohort of Italian Health Care Workers Receiving BNT162b2 mRNA Vaccine. Microorganisms 2021, 9, 1315 .
AMA StyleChiara Agrati, Concetta Castilletti, Delia Goletti, Silvia Meschi, Alessandra Sacchi, Giulia Matusali, Veronica Bordoni, Linda Petrone, Daniele Lapa, Stefania Notari, Valentina Vanini, Francesca Colavita, Alessandra Aiello, Alessandro Agresta, Chiara Farroni, Germana Grassi, Sara Leone, Francesco Vaia, Maria Capobianchi, Giuseppe Ippolito, Vincenzo Puro, on behalf of the INMI COVID-190 Vaccine Study Group. Coordinate Induction of Humoral and Spike Specific T-Cell Response in a Cohort of Italian Health Care Workers Receiving BNT162b2 mRNA Vaccine. Microorganisms. 2021; 9 (6):1315.
Chicago/Turabian StyleChiara Agrati; Concetta Castilletti; Delia Goletti; Silvia Meschi; Alessandra Sacchi; Giulia Matusali; Veronica Bordoni; Linda Petrone; Daniele Lapa; Stefania Notari; Valentina Vanini; Francesca Colavita; Alessandra Aiello; Alessandro Agresta; Chiara Farroni; Germana Grassi; Sara Leone; Francesco Vaia; Maria Capobianchi; Giuseppe Ippolito; Vincenzo Puro; on behalf of the INMI COVID-190 Vaccine Study Group. 2021. "Coordinate Induction of Humoral and Spike Specific T-Cell Response in a Cohort of Italian Health Care Workers Receiving BNT162b2 mRNA Vaccine." Microorganisms 9, no. 6: 1315.
Vaccination against SARS-CoV-2 is considered the most effective method of prevention to contain the pandemic. While highly effective SARS-CoV-2 vaccines are being applied on a large-scale, whether and to what extent the strength of the vaccine-induced immune response could be further potentiated is still an object of debate. Several reports studied the effect of different vaccines on the susceptibility and mortality of COVID-19, with conflicting results. We aimed to evaluate whether previous influenza and/or pneumococcal vaccination had an impact on the specific immune response to the SARS-CoV-2 BNT162b2 mRNA vaccine. The study population consists of 710 workers from our Institute who completed the BNT162b2 schedule and have been tested at least once after the second dose, from 27 December 2020 up to 15 April 2021. Of these, 152 (21.4%) had received an influenza and 215 (30.3%) a concomitant influenza and pneumococcal vaccination, a median of 102 days before the second dose of BNT162b2. Overall, 100% of workers were tested for anti-Spike receptor-binding domain (anti-S/RBD) antibodies, 224 workers for neutralization titer (Micro-neutralization assay, MNA), and 155 workers for a spike-specific T cell interferon-γ response (IFN-γ). The levels of anti-S/RBD, MNA and IFN-γ were evaluated and compared according to sex, age, involvement in direct care of COVID-19 patients, and previous influenza/pneumococcal vaccination. At the univariate analysis, no statistically significant association was observed with regard to a previous influenza and pneumococcal vaccination. A significant lower anti-S/RBD response was observed according to an older age and male sex, while MNA titers were significantly associated to sex but not to age. At the multivariable analysis, workers receiving a concomitant influenza and pneumococcal vaccination or only influenza showed a 58% (p 0.01) and 42% (p 0.07) increase in MNA titers, respectively, compared to those who did not receive an influenza/pneumococcal vaccination. Female workers showed an 81% MNA and a 44% anti-S/RBD increase compared to male workers (p< 0.001). Compared to workers aged 21 to 49 years, those aged 50 or older were associated with a reduction in the anti-S/RBD (16%; p 0.005), MNA (31%; p 0.019), and IFN.g (32%) immune response. Maintaining the influenza and pneumococcal immunization program for the coming season, in which COVID-19 could still be spreading, remains strongly recommended to protect those who are more vulnerable and to limit the potential burden of these infections on the healthcare system.
Vincenzo Puro; Concetta Castilletti; Chiara Agrati; Delia Goletti; Sara Leone; Alessandro Agresta; Eleonora Cimini; Eleonora Tartaglia; Rita Casetti; Francesca Colavita; Silvia Meschi; Giulia Matusali; Daniele Lapa; Saeid Najafi Fard; Alessandra Aiello; Chiara Farrone; Paola Gallì; Maria Capobianchi; Giuseppe Ippolito; on behalf of the INMI COVID-19 Vaccine Study Group. Impact of Prior Influenza and Pneumoccocal Vaccines on Humoral and Cellular Response to SARS-CoV-2 BNT162b2 Vaccination. Vaccines 2021, 9, 615 .
AMA StyleVincenzo Puro, Concetta Castilletti, Chiara Agrati, Delia Goletti, Sara Leone, Alessandro Agresta, Eleonora Cimini, Eleonora Tartaglia, Rita Casetti, Francesca Colavita, Silvia Meschi, Giulia Matusali, Daniele Lapa, Saeid Najafi Fard, Alessandra Aiello, Chiara Farrone, Paola Gallì, Maria Capobianchi, Giuseppe Ippolito, on behalf of the INMI COVID-19 Vaccine Study Group. Impact of Prior Influenza and Pneumoccocal Vaccines on Humoral and Cellular Response to SARS-CoV-2 BNT162b2 Vaccination. Vaccines. 2021; 9 (6):615.
Chicago/Turabian StyleVincenzo Puro; Concetta Castilletti; Chiara Agrati; Delia Goletti; Sara Leone; Alessandro Agresta; Eleonora Cimini; Eleonora Tartaglia; Rita Casetti; Francesca Colavita; Silvia Meschi; Giulia Matusali; Daniele Lapa; Saeid Najafi Fard; Alessandra Aiello; Chiara Farrone; Paola Gallì; Maria Capobianchi; Giuseppe Ippolito; on behalf of the INMI COVID-19 Vaccine Study Group. 2021. "Impact of Prior Influenza and Pneumoccocal Vaccines on Humoral and Cellular Response to SARS-CoV-2 BNT162b2 Vaccination." Vaccines 9, no. 6: 615.
SARS-CoV-2 serum neutralization assay represents the gold standard for assessing antibody-mediated protection in naturally infected and vaccinated individuals. In the present study, 662 serum samples collected from February 2020 to January 2021 from acute and convalescent COVID-19 patients were tested to determine neutralizing antibody (NAb) titers using a microneutralization test (MNT) for live SARS-CoV-2. Moreover, anti-SARS-CoV-2 IgG, IgA, and IgM directed against different viral antigens were measured by high-throughput automated platforms. We observed higher levels of NAbs in elderly (>60 years old) individuals and in patients presenting acute respiratory distress syndrome. SARS-CoV-2 NAbs develop as soon as five days from symptom onset and, despite a decline after the second month, persist for over 11 months, showing variable dynamics. Through correlation and receiver operating characteristic (ROC) curve analysis, we set up a testing algorithm, suitable for the laboratory workload, by establishing an optimal cutoff value of anti-SARS-CoV-2 IgG for convalescent plasma donors to exclude from MNT samples foreseen to have low/negative NAb titers and ineligible for plasma donation. Overall, MNT, although cumbersome and not suitable for routine testing of large sample sizes, remains the reference tool for the assessment of antibody-mediated immunity after SARS-CoV-2 infection. Smart testing algorithms may optimize the laboratory workflow to monitor antibody-mediated protection in COVID-19 patients, plasma donors, and vaccinated individuals.
Giulia Matusali; Francesca Colavita; Daniele Lapa; Silvia Meschi; Licia Bordi; Pierluca Piselli; Roberta Gagliardini; Angela Corpolongo; Emanuele Nicastri; Andrea Antinori; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus. Viruses 2021, 13, 655 .
AMA StyleGiulia Matusali, Francesca Colavita, Daniele Lapa, Silvia Meschi, Licia Bordi, Pierluca Piselli, Roberta Gagliardini, Angela Corpolongo, Emanuele Nicastri, Andrea Antinori, Giuseppe Ippolito, Maria Rosaria Capobianchi, Concetta Castilletti. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus. Viruses. 2021; 13 (4):655.
Chicago/Turabian StyleGiulia Matusali; Francesca Colavita; Daniele Lapa; Silvia Meschi; Licia Bordi; Pierluca Piselli; Roberta Gagliardini; Angela Corpolongo; Emanuele Nicastri; Andrea Antinori; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. 2021. "SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus." Viruses 13, no. 4: 655.
BackgroundIn Italy, dengue virus is the most frequent agent of imported viral infections. The use of rapid diagnostic tests (RDTs) may be of help as a preliminary user-friendly quick assay to facilitate dengue diagnosis, as ordinary laboratory diagnosis of dengue fever may require special efforts in terms of tools availability, interpretation of results, and skilled personnel. The performance of RDTs, however, may vary according to different epidemiological and laboratory background.MethodsWe reviewed five years of laboratory records of two dengue RDT results (Colorimetric SD-Bioline Dengue-Duo-RDT and Fluorimetric SD-Biosensor-STANDARD-F-Dengue-RDT), able to detect viral NS1 antigen and specific IgM and IgG. Diagnostic parameters were calculated using as reference the results of molecular (RT-PCR) and serological (immunofluorescence, IFA) tests. Overall performance, calculated considering the final case definition, was included in the accuracy assessment of RDTs.ResultsThe combined use of NS1 and IgM/IgG RDT for the detection of acute dengue cases resulted in an overall sensitivity and specificity of 87.2% and 97.9% for Colorimetric RDT, 96.2% and 96.2% for Fluorimetric RDT. NS1 was the most reliable marker of acute infection, while IgM resulted falsely positive in nine samples, including sera derived from 2 Zika and 4 non-arbovirus infected patients.ConclusionsThe inclusion of RDT in the diagnostic algorithm is of undeniable help in the prompt management and surveillance of dengue infection in non-endemic areas. Confirmatory tests are, however, necessary to rule in or rule out dengue fever diagnosis.
Giulia Matusali; Francesca Colavita; Fabrizio Carletti; Eleonora Lalle; Licia Bordi; Francesco Vairo; Giuseppe Ippolito; Maria R. Capobianchi; Concetta Castilletti. Performance of rapid tests in the management of dengue fever imported cases in Lazio, Italy 2014-2019. International Journal of Infectious Diseases 2020, 99, 193 -198.
AMA StyleGiulia Matusali, Francesca Colavita, Fabrizio Carletti, Eleonora Lalle, Licia Bordi, Francesco Vairo, Giuseppe Ippolito, Maria R. Capobianchi, Concetta Castilletti. Performance of rapid tests in the management of dengue fever imported cases in Lazio, Italy 2014-2019. International Journal of Infectious Diseases. 2020; 99 ():193-198.
Chicago/Turabian StyleGiulia Matusali; Francesca Colavita; Fabrizio Carletti; Eleonora Lalle; Licia Bordi; Francesco Vairo; Giuseppe Ippolito; Maria R. Capobianchi; Concetta Castilletti. 2020. "Performance of rapid tests in the management of dengue fever imported cases in Lazio, Italy 2014-2019." International Journal of Infectious Diseases 99, no. : 193-198.
Serological tests for anti-SARS-CoV-2 antibodies are becoming of great interest to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. We evaluated the diagnostic performance of the Abbott ARCHITECT SARS-CoV-2 IgG test, a fully automated indirect immunoassay that detects antibodies directed to a recombinant SARS-CoV-2 Nucleocapsid antigen. Abbott ARCHITECT SARS-CoV-2 IgG immunoassay was compared to an indirect immunofluorescence assay (IFA) on sera from patients with COVID-19 collected at different days after symptoms onset or infected by other human coronaviruses. Comparison with neutralization test was also performed. After 7, 14 and >14 days after onset ARCHITECT was positive on 8.3 %; 61.9 % and 100 % of the tested samples compared to 58.3 %; 85.7 % and 100 % by IFA. The sensitivity was 72 % vs. IFA and 66.7 % vs. a real-time PCR, the specificity was 100 %. On 18 samples with neutralizing activity, 17 were positive by Abbott ARCHITECT SARS-CoV-2 IgG. In our study, Abbott ARCHITECT SARS-CoV-2 IgG assay showed a satisfactory performance, with a very high specificity. IgG reactivity against SARSCoV-2 N antigen was detectable in all patients by two weeks after symptoms onset. In addition, concordance between this serological response and viral neutralization suggests that a strong humoral response may be predictive of a neutralization activity, regardless of the target antigens. This finding supports the use of this automated serological assay in diagnostic algorithm and public health intervention, especially for high loads of testing.
Silvia Meschi; Francesca Colavita; Licia Bordi; Giulia Matusali; Daniele Lapa; Alessandra Amendola; Francesco Vairo; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. Performance evaluation of Abbott ARCHITECT SARS-CoV-2 IgG immunoassay in comparison with indirect immunofluorescence and virus microneutralization test. Journal of Clinical Virology 2020, 129, 104539 -104539.
AMA StyleSilvia Meschi, Francesca Colavita, Licia Bordi, Giulia Matusali, Daniele Lapa, Alessandra Amendola, Francesco Vairo, Giuseppe Ippolito, Maria Rosaria Capobianchi, Concetta Castilletti. Performance evaluation of Abbott ARCHITECT SARS-CoV-2 IgG immunoassay in comparison with indirect immunofluorescence and virus microneutralization test. Journal of Clinical Virology. 2020; 129 ():104539-104539.
Chicago/Turabian StyleSilvia Meschi; Francesca Colavita; Licia Bordi; Giulia Matusali; Daniele Lapa; Alessandra Amendola; Francesco Vairo; Giuseppe Ippolito; Maria Rosaria Capobianchi; Concetta Castilletti. 2020. "Performance evaluation of Abbott ARCHITECT SARS-CoV-2 IgG immunoassay in comparison with indirect immunofluorescence and virus microneutralization test." Journal of Clinical Virology 129, no. : 104539-104539.
The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.
Anna Le Tortorec; Giulia Matusali; Dominique Mahé; Florence Aubry; Severine Mazaud-Guittot; Laurent Houzet; Nathalie Dejucq-Rainsford. From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract. Physiological Reviews 2020, 100, 1349 -1414.
AMA StyleAnna Le Tortorec, Giulia Matusali, Dominique Mahé, Florence Aubry, Severine Mazaud-Guittot, Laurent Houzet, Nathalie Dejucq-Rainsford. From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract. Physiological Reviews. 2020; 100 (3):1349-1414.
Chicago/Turabian StyleAnna Le Tortorec; Giulia Matusali; Dominique Mahé; Florence Aubry; Severine Mazaud-Guittot; Laurent Houzet; Nathalie Dejucq-Rainsford. 2020. "From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract." Physiological Reviews 100, no. 3: 1349-1414.
Serological assays for anti-SARS-CoV-2 antibodies are now of critical importance to support diagnosis, guide epidemiological intervention, and understand immune response to natural infection and vaccine administration. We developed and validated new anti-SARS-CoV-2 IgG, IgM and IgA ELISA tests (ENZY-WELL SARS-CoV-2 ELISA, DIESSE Diagnostica Senese S.p.a.) based on whole-virus antigens. We used a total of 553 serum samples including samples from COVID-19 suspected and confirmed cases, healthy donors, and patients positive for other infections or autoimmune conditions. Overall, the assays showed good concordance with the indirect immunofluorescence reference test in terms of sensitivity and specificity. Especially for IgG and IgA, we observed high sensitivity (92.5 and 93.6%, respectively); specificity was high (>96%) for all antibody types ELISAs. In addition, sensitivity was linked to the days from symptoms onset (DSO) due to the seroconversion window, and for ENZY-WELL SARS-CoV-2 IgG and IgA ELISAs resulted 100% in those samples collected after 10 and 12 DSO, respectively. The results showed that ENZY-WELL SARS-CoV-2 ELISAs may represent a valid option for both diagnostic and epidemiological purposes, covering all different antibody types developed in SARS-CoV-2 immune response.
Colavita Francesca; Brogi Alessandra; Lapa Daniele; Bordi Licia; Matusali Giulia; Meschi Silvia; Marsella Patrizia; Tesi Giulia; Bandini Tommaso; Di Caro Antonino; Capobianchi Maria Rosaria; Castilletti Concetta. Evaluation of ELISA tests for the qualitative determination of IgG, IgM and IgA to SARS-CoV-2. 2020, 1 .
AMA StyleColavita Francesca, Brogi Alessandra, Lapa Daniele, Bordi Licia, Matusali Giulia, Meschi Silvia, Marsella Patrizia, Tesi Giulia, Bandini Tommaso, Di Caro Antonino, Capobianchi Maria Rosaria, Castilletti Concetta. Evaluation of ELISA tests for the qualitative determination of IgG, IgM and IgA to SARS-CoV-2. . 2020; ():1.
Chicago/Turabian StyleColavita Francesca; Brogi Alessandra; Lapa Daniele; Bordi Licia; Matusali Giulia; Meschi Silvia; Marsella Patrizia; Tesi Giulia; Bandini Tommaso; Di Caro Antonino; Capobianchi Maria Rosaria; Castilletti Concetta. 2020. "Evaluation of ELISA tests for the qualitative determination of IgG, IgM and IgA to SARS-CoV-2." , no. : 1.
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus that displays a large cell and organ tropism, and causes a broad range of clinical symptoms in humans. It is maintained in nature through both urban and sylvatic cycles, involving mosquito vectors and human or vertebrate animal hosts. Although CHIKV was first isolated in 1953, its pathogenesis was only more extensively studied after its re-emergence in 2004. The unexpected spread of CHIKV to novel tropical and non-tropical areas, in some instances driven by newly competent vectors, evidenced the vulnerability of new territories to this infectious agent and its associated diseases. The comprehension of the exact CHIKV target cells and organs, mechanisms of pathogenesis, and spectrum of both competitive vectors and animal hosts is pivotal for the design of effective therapeutic strategies, vector control measures, and eradication actions.
Giulia Matusali; Francesca Colavita; Licia Bordi; Eleonora Lalle; Giuseppe Ippolito; Maria R. Capobianchi; Concetta Castilletti. Tropism of the Chikungunya Virus. Viruses 2019, 11, 175 .
AMA StyleGiulia Matusali, Francesca Colavita, Licia Bordi, Eleonora Lalle, Giuseppe Ippolito, Maria R. Capobianchi, Concetta Castilletti. Tropism of the Chikungunya Virus. Viruses. 2019; 11 (2):175.
Chicago/Turabian StyleGiulia Matusali; Francesca Colavita; Licia Bordi; Eleonora Lalle; Giuseppe Ippolito; Maria R. Capobianchi; Concetta Castilletti. 2019. "Tropism of the Chikungunya Virus." Viruses 11, no. 2: 175.
Zika virus (ZIKV) is a teratogenic mosquito-borne flavivirus that can be sexually transmitted from man to woman. The finding of high viral loads and prolonged viral shedding in semen suggests that ZIKV replicates within the human male genital tract, but its target organs are unknown. Using ex vivo infection of organotypic cultures, we demonstrated here that ZIKV replicates in human testicular tissue and infects a broad range of cell types, including germ cells, which we also identified as infected in semen from ZIKV-infected donors. ZIKV had no major deleterious effect on the morphology and hormonal production of the human testis explants. Infection induced a broad antiviral response but no IFN upregulation and minimal proinflammatory response in testis explants, with no cytopathic effect. Finally, we studied ZIKV infection in mouse testis and compared it to human infection. This study provides key insights into how ZIKV may persist in semen and alter semen parameters, as well as a valuable tool for testing antiviral agents.
Giulia Matusali; Laurent Houzet; Anne-Pascale Satie; Dominique Mahé; Florence Aubry; Thérèse Couderc; Julie Frouard; Salomé Bourgeau; Karim Bensalah; Sylvain Lavoué; Guillaume Joguet; Louis Bujan; André Cabié; Gleide F Avelar; Marc Lecuit; Anna Le Tortorec; Nathalie Dejucq-Rainsford. Zika virus infects human testicular tissue and germ cells. Journal of Clinical Investigation 2018, 128, 4697 -4710.
AMA StyleGiulia Matusali, Laurent Houzet, Anne-Pascale Satie, Dominique Mahé, Florence Aubry, Thérèse Couderc, Julie Frouard, Salomé Bourgeau, Karim Bensalah, Sylvain Lavoué, Guillaume Joguet, Louis Bujan, André Cabié, Gleide F Avelar, Marc Lecuit, Anna Le Tortorec, Nathalie Dejucq-Rainsford. Zika virus infects human testicular tissue and germ cells. Journal of Clinical Investigation. 2018; 128 (10):4697-4710.
Chicago/Turabian StyleGiulia Matusali; Laurent Houzet; Anne-Pascale Satie; Dominique Mahé; Florence Aubry; Thérèse Couderc; Julie Frouard; Salomé Bourgeau; Karim Bensalah; Sylvain Lavoué; Guillaume Joguet; Louis Bujan; André Cabié; Gleide F Avelar; Marc Lecuit; Anna Le Tortorec; Nathalie Dejucq-Rainsford. 2018. "Zika virus infects human testicular tissue and germ cells." Journal of Clinical Investigation 128, no. 10: 4697-4710.
The sexual transmission of viruses is responsible for the spread of multiple infectious diseases. Although the human immunodeficiency virus (HIV)/AIDS pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. In a substantial number of HIV-infected men, viral strains present in semen differ from the ones in blood, suggesting that HIV is locally produced within the genital tract. Such local production may be responsible for the persistence of HIV in semen despite effective antiretroviral therapy. In this study, we used single-genome amplification, amplicon sequencing ( env gene), and phylogenetic analyses to compare the genetic structures of simian immunodeficiency virus (SIV) populations across all the male genital organs and blood in intravenously inoculated cynomolgus macaques in the chronic stage of infection. Examination of the virus populations present in the male genital tissues of the macaques revealed compartmentalized SIV populations in testis, epididymis, vas deferens, seminal vesicles, and urethra. We found genetic similarities between the viral strains present in semen and those in epididymis, vas deferens, and seminal vesicles. The contribution of male genital organs to virus shedding in semen varied among individuals and could not be predicted based on their infection or proinflammatory cytokine mRNA levels. These data indicate that rather than a single source, multiple genital organs are involved in the release of free virus and infected cells into semen. These findings have important implications for our understanding of systemic virus shedding and persistence in semen and for the design of eradication strategies to access viral reservoirs. IMPORTANCE Semen is instrumental for the dissemination of viruses through sexual contacts. Worryingly, a number of systemic viruses, such as HIV, can persist in this body fluid in the absence of viremia. The local source(s) of virus in semen, however, remains unknown. To elucidate the anatomic origin(s) of the virus released in semen, we compared viral populations present in semen with those in the male genital organs and blood of the Asian macaque model, using single-genome amplification, amplicon sequencing ( env gene), and phylogenetic analysis. Our results show that multiple genital tissues harbor compartmentalized strains, some of them (i.e., from epididymis, vas deferens, and seminal vesicles) displaying genetic similarities with the viral populations present in semen. This study is the first to uncover local genital sources of viral populations in semen, providing a new basis for innovative targeted strategies to prevent and eradicate HIV in the male genital tract.
Laurent Houzet; Marcos Pérez-Losada; Giulia Matusali; Claire Deleage; Nathalie Dereuddre-Bosquet; Anne-Pascale Satie; Florence Aubry; Emmanuelle Becker; Bernard Jégou; Roger Le Grand; Brandon F. Keele; Keith A. Crandall; Nathalie Dejucq-Rainsford. Seminal Simian Immunodeficiency Virus in Chronically Infected Cynomolgus Macaques Is Dominated by Virus Originating from Multiple Genital Organs. Journal of Virology 2018, 92, e00133-18 .
AMA StyleLaurent Houzet, Marcos Pérez-Losada, Giulia Matusali, Claire Deleage, Nathalie Dereuddre-Bosquet, Anne-Pascale Satie, Florence Aubry, Emmanuelle Becker, Bernard Jégou, Roger Le Grand, Brandon F. Keele, Keith A. Crandall, Nathalie Dejucq-Rainsford. Seminal Simian Immunodeficiency Virus in Chronically Infected Cynomolgus Macaques Is Dominated by Virus Originating from Multiple Genital Organs. Journal of Virology. 2018; 92 (14):e00133-18.
Chicago/Turabian StyleLaurent Houzet; Marcos Pérez-Losada; Giulia Matusali; Claire Deleage; Nathalie Dereuddre-Bosquet; Anne-Pascale Satie; Florence Aubry; Emmanuelle Becker; Bernard Jégou; Roger Le Grand; Brandon F. Keele; Keith A. Crandall; Nathalie Dejucq-Rainsford. 2018. "Seminal Simian Immunodeficiency Virus in Chronically Infected Cynomolgus Macaques Is Dominated by Virus Originating from Multiple Genital Organs." Journal of Virology 92, no. 14: e00133-18.
International audienceBACKGROUND: Evidence of human sexual transmission during Zika virus emergence is a matter of concern, particularly in procreation, but to date, kinetics of seminal shedding and the effects of infection on human reproductive function have not been described. To investigate the effects of Zika virus infection on semen and clearance of Zika virus from semen and body fluids, we aimed to study a cohort of Zika virus-infected men. METHODS: This prospective observational study recruited men presenting with acute Zika virus infection at Pointe-à-Pitre University Hospital in Guadeloupe, French Caribbean, where a Zika virus outbreak occurred between April and November, 2016. Blood, urine, and semen were collected at days 7, 11, 20, 30, 60, 90, and 120 after symptom onset, and semen characteristics, such as total sperm count, sperm motility, vitality, and morphology, and reproductive hormone concentrations, such as testosterone, inhibin, follicle-stimulating hormone, and luteinising hormone, were assessed. At days 7, 11, and 20, semen was processed to isolate motile spermatozoa. Zika virus RNA was detected by RT-PCR using whole blood, serum, urine, seminal plasma, semen cells, and motile spermatozoa fractions. Zika virus was isolated from different sperm fractions on Vero E6 cultures. FINDINGS: 15 male volunteers (mean age 35 years [SD 5; range 25-44) with acute Zika virus infection and positive Zika virus RNA detection in blood or urine were enrolled. Total sperm count was decreased from median 119 × 10(6) spermatozoa (IQR 22-234) at day 7 to 45·2 × 10(6) (16·5-89·6) at day 30 and 70 × 10(6) (28·5-81·4) at day 60, respectively, after Zika virus infection. Inhibin values increased from 93·5 pg/mL (IQR 55-162) at day 7 to 150 pg/mL (78-209) at day 120 when total sperm count recovered. In motile spermatozoa obtained after density gradient separation, Zika virus RNA was found in three of 14 patients at day 7, four of 15 at day 11, and four of 15 at day 20, and replication-competent virus was found in the tested patient. Seminal shedding kinetics seemed heterogeneous among patients. Whole blood was the fluid most frequently positive for Zika virus RNA (62 of 92 samples) and three patients remained positive at day 120. INTERPRETATION: Semen alterations early after acute Zika virus infection might affect fertility and could be explained by virus effects on the testis and epididymis. Frequency of shedding and high viral load in semen, together with the presence of replicative virus in a motile spermatozoa fraction, can lead to Zika virus transmission during sexual contact and assisted reproduction procedures. Whole blood seems to be the best specimen for Zika virus RNA detection, diagnosis, and follow-up. FUNDING: Agence de la Biomédecine/Agence Régionale de Santé de la Guadeloupe/Inserm-REACTing
Guillaume Joguet; Jean-Michel Mansuy; Giulia Matusali; Safouane Hamdi; Marie Walschaerts; Lynda Pavili; Stefanie Guyomard; Nadia Prisant; Pierre Lamarre; Nathalie Dejucq-Rainsford; Christophe Pasquier; Louis Bujan. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. The Lancet Infectious Diseases 2017, 17, 1200 -1208.
AMA StyleGuillaume Joguet, Jean-Michel Mansuy, Giulia Matusali, Safouane Hamdi, Marie Walschaerts, Lynda Pavili, Stefanie Guyomard, Nadia Prisant, Pierre Lamarre, Nathalie Dejucq-Rainsford, Christophe Pasquier, Louis Bujan. Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. The Lancet Infectious Diseases. 2017; 17 (11):1200-1208.
Chicago/Turabian StyleGuillaume Joguet; Jean-Michel Mansuy; Giulia Matusali; Safouane Hamdi; Marie Walschaerts; Lynda Pavili; Stefanie Guyomard; Nadia Prisant; Pierre Lamarre; Nathalie Dejucq-Rainsford; Christophe Pasquier; Louis Bujan. 2017. "Effect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study." The Lancet Infectious Diseases 17, no. 11: 1200-1208.
Semen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4 T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV-infected men can influence the ability of semen to enhance infection.
Céline Camus; Giulia Matusali; Olivier Bourry; Dominique Mahe; Florence Aubry; Louis Bujan; Christophe Pasquier; Patrice Massip; Célia Ravel; Onofrio Zirafi; Jan Munch; Nadia R. Roan; Charles Pineau; Nathalie Dejucq-Rainsford. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection. AIDS 2016, 30, 1197 -1208.
AMA StyleCéline Camus, Giulia Matusali, Olivier Bourry, Dominique Mahe, Florence Aubry, Louis Bujan, Christophe Pasquier, Patrice Massip, Célia Ravel, Onofrio Zirafi, Jan Munch, Nadia R. Roan, Charles Pineau, Nathalie Dejucq-Rainsford. Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection. AIDS. 2016; 30 (8):1197-1208.
Chicago/Turabian StyleCéline Camus; Giulia Matusali; Olivier Bourry; Dominique Mahe; Florence Aubry; Louis Bujan; Christophe Pasquier; Patrice Massip; Célia Ravel; Onofrio Zirafi; Jan Munch; Nadia R. Roan; Charles Pineau; Nathalie Dejucq-Rainsford. 2016. "Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T-cell infection." AIDS 30, no. 8: 1197-1208.
A number of men receiving prolonged suppressive highly active antiretroviral therapy (HAART) still shed human immunodeficiency virus (HIV) in semen. To investigate whether this seminal shedding may be due to poor drug penetration and/or viral production by long-lived cells within male genital tissues, we analyzed semen and reproductive tissues from macaques chronically infected with simian immunodeficiency virus mac251 (SIVmac251) who were treated for 4 months with HAART, which was intensified over the last 7 weeks with an integrase inhibitor. We showed that a subset of treated animals continued shedding SIV in semen despite efficient HAART. This shedding was not associated with low antiretroviral drug concentrations in semen or in testis, epididymis, seminal vesicles, and prostate. HAART had no significant impact on SIV RNA in the urethra, whereas it drastically reduced SIV RNA levels in the prostate and vas deferens and to a lesser extent in the epididymis and seminal vesicle. The only detectable SIV RNA-positive cells within the male genital tract after HAART were urethral macrophages. SIV DNA levels in genital tissues were not decreased by HAART, suggesting the presence throughout the male genital tract of nonproductively infected cells. In conclusion, our results demonstrate that 4 months of HAART induced variable and limited control of viral infection in the male reproductive organs, particularly in the urethra, and suggest that infected long-lived cells in the male genital tract may be involved in persistent seminal shedding during HAART. These results pave the way for further investigations of male genital organ infection in long-term-treated infected individuals. IMPORTANCE A substantial subset of men receiving prolonged HAART suppressing viral loads in the blood still harbor HIV in semen, and cases of sexual transmission have been reported. To understand the origin of this persistence, we analyzed the semen and male reproductive tissues from SIV-infected macaques treated with HAART. We demonstrated that persistent seminal shedding was not linked to poor drug penetration in semen or semen-producing prostate, seminal vesicle, epididymis, and testis. We revealed that HAART decreased SIV RNA to various extents in all male genital organs, with the exception of the urethra, in which SIV RNA + macrophages were observed despite HAART. Importantly, HAART did not impact SIV DNA levels in the male genital organs. These results suggest that infection of male genital organs, and particularly the urethra, could be involved in the release of virus in semen during HAART.
G. Matusali; N. Dereuddre-Bosquet; A. Le Tortorec; M. Moreau; A.-P. Satie; D. Mahé; P. Roumaud; O. Bourry; N. Sylla; S. Bernard-Stoecklin; A. Pruvost; R. Le Grand; N. Dejucq-Rainsford. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy. Journal of Virology 2015, 89, 5772 -5787.
AMA StyleG. Matusali, N. Dereuddre-Bosquet, A. Le Tortorec, M. Moreau, A.-P. Satie, D. Mahé, P. Roumaud, O. Bourry, N. Sylla, S. Bernard-Stoecklin, A. Pruvost, R. Le Grand, N. Dejucq-Rainsford. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy. Journal of Virology. 2015; 89 (11):5772-5787.
Chicago/Turabian StyleG. Matusali; N. Dereuddre-Bosquet; A. Le Tortorec; M. Moreau; A.-P. Satie; D. Mahé; P. Roumaud; O. Bourry; N. Sylla; S. Bernard-Stoecklin; A. Pruvost; R. Le Grand; N. Dejucq-Rainsford. 2015. "Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy." Journal of Virology 89, no. 11: 5772-5787.
Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers.
Laurent Houzet; Giulia Matusali; Nathalie Dejucq-Rainsford. Origins of HIV-infected Leukocytes and Virions in Semen. The Journal of Infectious Diseases 2014, 210, S622 -S630.
AMA StyleLaurent Houzet, Giulia Matusali, Nathalie Dejucq-Rainsford. Origins of HIV-infected Leukocytes and Virions in Semen. The Journal of Infectious Diseases. 2014; 210 (suppl 3):S622-S630.
Chicago/Turabian StyleLaurent Houzet; Giulia Matusali; Nathalie Dejucq-Rainsford. 2014. "Origins of HIV-infected Leukocytes and Virions in Semen." The Journal of Infectious Diseases 210, no. suppl 3: S622-S630.
Viral infection may induce the cell-surface expression of PVR (CD155) that, upon recognition by its cognate activating DNAM-1 receptor present on cytotoxic lymphocytes, may promote antiviral immune responses. Here we show that expression of the human immunodeficiency virus type 1 (HIV-1) Vpr protein in Jurkat T cells increases cell-surface and total PVR levels. Analysis of mutated Vpr variants indicated that Vpr uses the same protein surfaces, and hence probably the same mechanisms, to upregulate PVR and arrest the cell cycle in the G2 phase. Moreover, we found that PVR upregulation by Vpr relied on the ability of the protein to activate the ATR kinase that triggers the DNA damage response pathway and G2 arrest. Finally, we showed that Vpr contributes to PVR up-modulation in HIV-infected CD4+ T lymphocytes and inhibits the PVR downregulating activity of the viral Nef protein.
Lia Vassena; Erica Giuliani; Giulia Matusali; Éric A. Cohen; Margherita Doria. The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway. Journal of General Virology 2013, 94, 2664 -2669.
AMA StyleLia Vassena, Erica Giuliani, Giulia Matusali, Éric A. Cohen, Margherita Doria. The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway. Journal of General Virology. 2013; 94 (12):2664-2669.
Chicago/Turabian StyleLia Vassena; Erica Giuliani; Giulia Matusali; Éric A. Cohen; Margherita Doria. 2013. "The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway." Journal of General Virology 94, no. 12: 2664-2669.
In humans, the interaction of the natural killer group 2 member D (NKG2D)-activating receptor on natural killer (NK) and CD8+ T cells with its major histocompatibility complex class I-related chain (MIC) and UL16 binding protein (ULBP) ligands (NKG2DLs) promotes recognition and elimination of stressed cells, such as tumor or infected cells. Here, we investigated the capacity of HIV-1 to modulate NKG2DL expression and escape NGK2D-mediated immunosurveillance. In CD4+ T lymphocytes, both cell surface expression and release of MICA, MICB, and ULBP2 were up-regulated >2-fold by HIV-1 infection. In HIV-infected CD4+ T lymphocytes or Jurkat T-cell lines, increased shedding of soluble NKG2DLs (sNKG2DLs) was impaired by a matrix metalloproteinase inhibitor (MMPI). Moreover, naive HIV+ patients displayed increased plasma sMICA and sULBP2 levels and reduced NKG2D expression on NK and CD8+ T cells compared to patients receiving highly active antiretroviral therapy (HAART) or healthy donors. In individual patients, HAART uptake resulted in the drop of sNKG2DL and recovery of NKG2D expression. Finally, sNKG2DLs in patients' plasma down-regulated NKG2D on NK and CD8+ T cells and impaired NKG2D-mediated cytotoxicity of NK cells. Thus, NKG2D detuning by sNKG2DLs may promote HIV-1 immune evasion and compromise host resistance to opportunistic infections, but HAART and MMPI have the potential to avoid such immune dysfunction.—Matusali, G., Tchidjou, H. K., Pontrelli, G., Bernardi, S., D'Ettorre, G., Vullo, V., Buonomini, A. R., Andreoni, M., Santoni, A., Cerboni, C., Doria, M. Soluble ligands for the NKG2D receptor are released during HIV-1 infection and impair NKG2D expression and cytotoxicity of NK cells.
Giulia Matusali; Hyppolite Kuekou Tchidjou; Giuseppe Pontrelli; Stefania Bernardi; Gabriella D'Ettorre; Vincenzo Vullo; Anna Rita Buonomini; Massimo Andreoni; Angela Santoni; Cristina Cerboni; Margherita Doria. Soluble ligands for the NKG2D receptor are released during HIV‐1 infection and impair NKG2D expression and cytotoxicity of NK cells. The FASEB Journal 2013, 27, 2440 -2450.
AMA StyleGiulia Matusali, Hyppolite Kuekou Tchidjou, Giuseppe Pontrelli, Stefania Bernardi, Gabriella D'Ettorre, Vincenzo Vullo, Anna Rita Buonomini, Massimo Andreoni, Angela Santoni, Cristina Cerboni, Margherita Doria. Soluble ligands for the NKG2D receptor are released during HIV‐1 infection and impair NKG2D expression and cytotoxicity of NK cells. The FASEB Journal. 2013; 27 (6):2440-2450.
Chicago/Turabian StyleGiulia Matusali; Hyppolite Kuekou Tchidjou; Giuseppe Pontrelli; Stefania Bernardi; Gabriella D'Ettorre; Vincenzo Vullo; Anna Rita Buonomini; Massimo Andreoni; Angela Santoni; Cristina Cerboni; Margherita Doria. 2013. "Soluble ligands for the NKG2D receptor are released during HIV‐1 infection and impair NKG2D expression and cytotoxicity of NK cells." The FASEB Journal 27, no. 6: 2440-2450.
Giulia Matusali; Valentina Pacciani; Federica Angelini; Viviana Moschese; Loredana Chini; Margherita Doria. Plasma levels of soluble MICA and ULBP2 are increased in children allergic to dust mites. Journal of Allergy and Clinical Immunology 2012, 130, 1003 -1005.
AMA StyleGiulia Matusali, Valentina Pacciani, Federica Angelini, Viviana Moschese, Loredana Chini, Margherita Doria. Plasma levels of soluble MICA and ULBP2 are increased in children allergic to dust mites. Journal of Allergy and Clinical Immunology. 2012; 130 (4):1003-1005.
Chicago/Turabian StyleGiulia Matusali; Valentina Pacciani; Federica Angelini; Viviana Moschese; Loredana Chini; Margherita Doria. 2012. "Plasma levels of soluble MICA and ULBP2 are increased in children allergic to dust mites." Journal of Allergy and Clinical Immunology 130, no. 4: 1003-1005.
The human immunodeficiency virus type 1 (HIV-1) evades the immune responses of natural killer (NK) cells through mechanisms that have been partially deciphered. Here we show that in HIV-1-infected T lymphocytes, the early viral Nef protein downmodulates PVR (CD155, Necl-5), a ligand for the activating receptor DNAM-1 (CD226) expressed by all NK cells, CD8+ T cells, and other cell types. This novel Nef activity is conserved by Nef proteins of laboratory HIV-1 strains (NL4-3, SF2) and of a patient-derived virus, but it is not maintained by HIV-2. Nef uses the same motifs to downregulate PVR and HLA-I molecules, likely by the same mechanisms. Indeed, as previously demonstrated for HLA-I, Nef reduces the total amounts of cell-associated PVR. Optimal downregulation of cell surface PVR by Nef also requires the presence of the late viral factor Vpu. In line with PVR reduction, the NK cell-mediated lysis of T cells infected by a wild-type but not Nef-deficient virus is virtually abrogated upon blocking of both DNAM-1 and another activating receptor, NKG2D, previously shown to mediate killing of HIV-infected cells. Together, these data demonstrate that the PVR downmodulation by Nef and Vpu is a strategy evolved by HIV-1 to prevent NK cell-mediated lysis of infected cells. The PVR downregulation reported here has the potential to affect the immune responses of other DNAM-1-positive cells besides NK cells and to alter multiple PVR-mediated cellular processes, such as adhesion and migration, and may thus greatly influence HIV-1 pathogenesis.
Giulia Matusali; Marina Potestà; Angela Santoni; Cristina Cerboni; Margherita Doria. The Human Immunodeficiency Virus Type 1 Nef and Vpu Proteins Downregulate the Natural Killer Cell-Activating Ligand PVR. Journal of Virology 2012, 86, 4496 -4504.
AMA StyleGiulia Matusali, Marina Potestà, Angela Santoni, Cristina Cerboni, Margherita Doria. The Human Immunodeficiency Virus Type 1 Nef and Vpu Proteins Downregulate the Natural Killer Cell-Activating Ligand PVR. Journal of Virology. 2012; 86 (8):4496-4504.
Chicago/Turabian StyleGiulia Matusali; Marina Potestà; Angela Santoni; Cristina Cerboni; Margherita Doria. 2012. "The Human Immunodeficiency Virus Type 1 Nef and Vpu Proteins Downregulate the Natural Killer Cell-Activating Ligand PVR." Journal of Virology 86, no. 8: 4496-4504.