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Dr. Levon Abrahamyan
Department of Pathology and Microbiology, Faculty of Veterinary Medicine, University of Montreal, Montreal, QС J2S 2M2, Canada

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Original research article
Published: 05 August 2021 in Frontiers in Veterinary Science
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African swine fever (ASF) is an emerging viral contagious disease affecting domestic pigs (DP) and wild boar (WB). ASF causes significant economic damage to the pig industry worldwide due to nearly 100% mortality and the absence of medical treatments. Since 2019, an intensive spread of ASF has been observed in the Russian Far East region. This spread raises concerns for epidemiologists and ecologists given the potential threat to the WB population, which is an essential member of the region's wild ungulates and provides a notable share of food resources for predatory species. This study aims to determine the genotype of ASF virus circulating in the region, reveal the spatio-temporal patterns of the ASF outbreaks' emergence, and assess the potential reduction of the regional fauna because of expected depopulation of WB. The first historical case of ASF in the study region was caused by an African swine fever virus (ASFV) isolated from DPs and belonging to Genotype 2, CVR1; IGR-2 (TRS +). Sequencing results showed no significant differences among ASFV strains currently circulating in the Russian Federation, Europe, and China. The spatiotemporal analysis with the space-time permutations model demonstrated the presence of six statistically significant clusters of ASF outbreaks with three clusters in DPs and one cluster in WBs. DP outbreaks prevail in the north-west regions of the study area, while northern regions demonstrate a mixture of DP and WB outbreaks. Colocation analysis did not reveal a statistically significant pattern of grouping of one category of outbreaks around the others. The possible damage to the region's fauna was assessed by modeling the total body mass of wild ungulates before and after the wild boars' depopulation, considering a threshold density of WB population of 0.025 head/km2, according to the currently in force National Plan on the ASF Eradication in Russia. The results suggest the total mass of ungulates of the entire study region will likely decrease by 8.4% (95% CI: 4.1–13.0%), while it may decrease by 33.6% (19.3–46.1%) in the Primorsky Krai, thereby posing an undeniable threat to the predatory species of the region.

ACS Style

Olga I. Zakharova; Ilya A. Titov; Andrey E. Gogin; Timofey A. Sevskikh; Fedor I. Korennoy; Denis V. Kolbasov; Levon Abrahamyan; Andrey A. Blokhin. African Swine Fever in the Russian Far East (2019–2020): Spatio-Temporal Analysis and Implications for Wild Ungulates. Frontiers in Veterinary Science 2021, 8, 1 .

AMA Style

Olga I. Zakharova, Ilya A. Titov, Andrey E. Gogin, Timofey A. Sevskikh, Fedor I. Korennoy, Denis V. Kolbasov, Levon Abrahamyan, Andrey A. Blokhin. African Swine Fever in the Russian Far East (2019–2020): Spatio-Temporal Analysis and Implications for Wild Ungulates. Frontiers in Veterinary Science. 2021; 8 ():1.

Chicago/Turabian Style

Olga I. Zakharova; Ilya A. Titov; Andrey E. Gogin; Timofey A. Sevskikh; Fedor I. Korennoy; Denis V. Kolbasov; Levon Abrahamyan; Andrey A. Blokhin. 2021. "African Swine Fever in the Russian Far East (2019–2020): Spatio-Temporal Analysis and Implications for Wild Ungulates." Frontiers in Veterinary Science 8, no. : 1.

Review article
Published: 03 March 2020 in Critical Reviews in Microbiology
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Cell culture-based vaccine technology is a flexible and convenient approach for vaccine production that requires adaptation of the vaccine strains to the new cells. Driven by the motivation to develop a broadly permissive cell line for infection with a wide range of viruses, we identified a set of the most relevant host receptors involved in viral attachment and entry. This identification was done through a review of different viral entry pathways and host cell lines, and in the context of the Baltimore classification of viruses. In addition, we indicated the potential technical problems and proposed some solutions regarding how to modify the host cell genome in order to meet industrial requirements for mass production of antiviral vaccines. Our work contributes to a finer understanding of the importance of breaking the host–virus recognition specificities for the possibility of creating a cell line feasible for the production of vaccines against a broad spectrum of viruses.

ACS Style

Xiaofeng Dai; Xuanhao Zhang; Kostya Ostrikov; Levon Abrahamyan. Host receptors: the key to establishing cells with broad viral tropism for vaccine production. Critical Reviews in Microbiology 2020, 46, 147 -168.

AMA Style

Xiaofeng Dai, Xuanhao Zhang, Kostya Ostrikov, Levon Abrahamyan. Host receptors: the key to establishing cells with broad viral tropism for vaccine production. Critical Reviews in Microbiology. 2020; 46 (2):147-168.

Chicago/Turabian Style

Xiaofeng Dai; Xuanhao Zhang; Kostya Ostrikov; Levon Abrahamyan. 2020. "Host receptors: the key to establishing cells with broad viral tropism for vaccine production." Critical Reviews in Microbiology 46, no. 2: 147-168.

Article
Published: 26 November 2019 in BioNanoScience
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The expression of activation markers on lymphocytes and a subpopulation of regulatory T cells (CD4+ CD25+ Hi) were evaluated in children with chronic pyelonephritis. We have distinguished the following clinical variants of pathology: dysmetabolic, obstructive, and mixed (obstructive dysmetabolic) chronic pyelonephritis. Flow cytofluorometry was used to evaluate the population and subpopulations of T lymphocytes expressing CD3+HLA-DR+ and CD8+HLA-DR+ class II histocompatibility antigens, CD95−СD3+CD95+ activation apoptosis marker, subpopulations expressing the homing receptor CD4+CD62L+ and CD4+CD62L−, and subpopulations of CD4+CD25+Hi regulatory T cells (Treg). In dysmetabolic variants of chronic pyelonephritis, an activation profile of lymphocytes is characterized mainly by positive activation and the subpopulation of CD4+ lymphocytes, forming an increase in the content of effectors/activated cells with enhanced migration into the target organ. In the case of obstructive variants of chronic pyelonephritis, antigen-mediated activation and an increase in the pool of activated cytotoxic T lymphocytes (CD8+HLA-DR+) result in activation-induced apoptosis and cell death, leading to leukopenia and lymphopenia. Expansion of regulatory T cells (CD4+CD25+ Hi) in obstructive variants of chronic pyelonephritis can be considered a factor regulating apoptosis in the process of long-term activation of T lymphocytes.

ACS Style

Elena V. Agafonova; Farida F. Rizvanova; Tatyana G. Malanicheva; Levon Abrahamyan. Activation Markers and Regulatory T cells in Children with Chronic Pyelonephritis Associated with Bacterial Uropathogens. BioNanoScience 2019, 1 -7.

AMA Style

Elena V. Agafonova, Farida F. Rizvanova, Tatyana G. Malanicheva, Levon Abrahamyan. Activation Markers and Regulatory T cells in Children with Chronic Pyelonephritis Associated with Bacterial Uropathogens. BioNanoScience. 2019; ():1-7.

Chicago/Turabian Style

Elena V. Agafonova; Farida F. Rizvanova; Tatyana G. Malanicheva; Levon Abrahamyan. 2019. "Activation Markers and Regulatory T cells in Children with Chronic Pyelonephritis Associated with Bacterial Uropathogens." BioNanoScience , no. : 1-7.

Journal article
Published: 01 September 2019 in Journal of Zoo and Wildlife Medicine
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An onset of respiratory disease in a captive bachelor group (n = 3) of western lowland gorillas (Gorilla gorilla gorilla) was concomitant with peak attendance of visitors at the institution and with unwanted occurrences of food items being thrown in the gorillas' enclosure. While the condition of two individuals improved with supportive therapy and antibiotics, the third gorilla died three days following initiation of treatment. A fatal bacterial pneumonia, secondary to an infection by a human parainfluenza virus 2 (HIPV-2), was considered to be the cause of death based on histopathology, lung cultures, and reverse transcription PCR. HPIV-2 activity in the human population of the province was detected for that period, including the same viral strain. This report confirms a HPIV-2 respiratory illness and associated death in a gorilla. Clinical presentation and context suggest conspecifics were also affected and that contaminated food thrown by visitors may have been the source of infection.

ACS Style

Émilie L. Couture; Shannon T. Ferrell; Marion Desmarchelier; Marie-Ève Hamelin; Laura Jhoana Sánchez Mendoza; Julie Carbonneau; Levon Abrahamyan; Guy Boivin; Stéphane Lair. HUMAN PARAINFLUENZA 2 RELATED ILLNESS AND A DEATH IN A GROUP OF CAPTIVE WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA). Journal of Zoo and Wildlife Medicine 2019, 50, 713 -717.

AMA Style

Émilie L. Couture, Shannon T. Ferrell, Marion Desmarchelier, Marie-Ève Hamelin, Laura Jhoana Sánchez Mendoza, Julie Carbonneau, Levon Abrahamyan, Guy Boivin, Stéphane Lair. HUMAN PARAINFLUENZA 2 RELATED ILLNESS AND A DEATH IN A GROUP OF CAPTIVE WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA). Journal of Zoo and Wildlife Medicine. 2019; 50 (3):713-717.

Chicago/Turabian Style

Émilie L. Couture; Shannon T. Ferrell; Marion Desmarchelier; Marie-Ève Hamelin; Laura Jhoana Sánchez Mendoza; Julie Carbonneau; Levon Abrahamyan; Guy Boivin; Stéphane Lair. 2019. "HUMAN PARAINFLUENZA 2 RELATED ILLNESS AND A DEATH IN A GROUP OF CAPTIVE WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA)." Journal of Zoo and Wildlife Medicine 50, no. 3: 713-717.

Journal article
Published: 31 March 2018 in Viruses
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The mechanism used by mouse polyomavirus (MPyV) to overcome the crowded cytosol to reach the nucleus has not been fully elucidated. Here, we investigated the involvement of importin α/β1 mediated transport in the delivery of MPyV genomes into the nucleus. Interactions of the virus with importin β1 were studied by co-immunoprecipitation and proximity ligation assay. For infectivity and nucleus delivery assays, the virus and its capsid proteins mutated in the nuclear localization signals (NLSs) were prepared and produced. We found that at early times post infection, virions bound importin β1 in a time dependent manner with a peak of interactions at 6 h post infection. Mutation analysis revealed that only when the NLSs of both VP1 and VP2/3 were disrupted, virus did not bind efficiently to importin β1 and its infectivity remarkably decreased (by 80%). Nuclear targeting of capsid proteins was improved when VP1 and VP2 were co-expressed. VP1 and VP2 were effectively delivered into the nucleus, even when one of the NLS, either VP1 or VP2, was disrupted. Altogether, our results showed that MPyV virions can use VP1 and/or VP2/VP3 NLSs in concert or individually to bind importins to deliver their genomes into the cell nucleus.

ACS Style

Irina Soldatova; Terezie Prilepskaja; Levon Abrahamyan; Jitka Forstová; Sandra Huérfano. Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus. Viruses 2018, 10, 165 .

AMA Style

Irina Soldatova, Terezie Prilepskaja, Levon Abrahamyan, Jitka Forstová, Sandra Huérfano. Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus. Viruses. 2018; 10 (4):165.

Chicago/Turabian Style

Irina Soldatova; Terezie Prilepskaja; Levon Abrahamyan; Jitka Forstová; Sandra Huérfano. 2018. "Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus." Viruses 10, no. 4: 165.

Article
Published: 13 January 2018 in BioNanoScience
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Biomedical advances have led to a relaxation of natural selection in the human population of developed countries. In the absence of strong purifying selection, spontaneous and frequently deleterious mutations tend to accumulate in the human genome and gradually increase the genetic load; that is, the frequency of potentially lethal genes in the gene pool. Gradual increase in incidence of many complex disorders suggests deleterious impact of the genetic load on human well-being. Recent advances in in vitro fertilization (IVF) combined with artificial twinning and transgenerational embryo cryoconservation offer the possibility of preventing significant accumulation of genetic load and reducing the incidence of hereditary disorders. Many complex diseases such as type 1 and 2 diabetes, autism, bipolar disorder, allergies, Alzheimer’s disease, and some cancers show significantly higher concordance in monozygotic (MZ) twins than in fraternal twins (dizygotic, DZ) or parent-child pairs, suggesting their etiology is strongly influenced by genetics. Preventing these diseases based on genetic data alone is frequently impossible due to the complex interplay between genetic and environmental factors. We hypothesize that the incidence of complex diseases could be significantly reduced in the future through a strategy based on time-separated twinning. This strategy involves the collection and fertilization of human oocytes followed by several rounds of artificial twinning. If preimplantation genetic screening (PGS) reports no aneuploidy or known Mendelian disorders, one of the MZ siblings would be implanted and the remaining embryos cryoconserved. Once the good health of the adult MZ sibling(s) is established, subsequent parenthood with the cryoconserved co-twins could substantially lower the incidence of hereditary disorders with complex etiology and virtually eradicate simple Mendelian disorders. The proposed method of artificial twinning has the potential to alleviate suffering and reduce the negative social impact induced by dysgenic effects associated with known and unknown genetic factors. Time-separated twinning has the capacity to prevent further accumulation of the genetic load and to provide source of isogenic embryonic stem cells for future regenerative therapies.

ACS Style

Alexander Churbanov; Levon Abrahamyan. Preventing Common Hereditary Disorders through Time-Separated Twinning. BioNanoScience 2018, 8, 344 -366.

AMA Style

Alexander Churbanov, Levon Abrahamyan. Preventing Common Hereditary Disorders through Time-Separated Twinning. BioNanoScience. 2018; 8 (1):344-366.

Chicago/Turabian Style

Alexander Churbanov; Levon Abrahamyan. 2018. "Preventing Common Hereditary Disorders through Time-Separated Twinning." BioNanoScience 8, no. 1: 344-366.

Editorial
Published: 14 December 2017 in Journal of Immunology Research
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ACS Style

Sergey Morzunov; Varough Deyde; Levon Abrahamyan. New Biomarkers of Innate and Adaptive Immunity in Infectious Diseases. Journal of Immunology Research 2017, 2017, 1 -3.

AMA Style

Sergey Morzunov, Varough Deyde, Levon Abrahamyan. New Biomarkers of Innate and Adaptive Immunity in Infectious Diseases. Journal of Immunology Research. 2017; 2017 ():1-3.

Chicago/Turabian Style

Sergey Morzunov; Varough Deyde; Levon Abrahamyan. 2017. "New Biomarkers of Innate and Adaptive Immunity in Infectious Diseases." Journal of Immunology Research 2017, no. : 1-3.

Erratum
Published: 20 September 2017 in Veterinary Research
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After publication of the article [1], it has been brought to our attention that an acknowledgement has been omitted from the original article. The authors would like to include the following, The authors also thank Prof. En-Min Zhou (Northwest A&F University) and his laboratory for technical support.”

ACS Style

Chengbao Wang; Han Meng; Yujin Gao; Hui Gao; Kangkang Guo; Fernando Almazan; Isabel Sola; Luis Enjuanes; Yanming Zhang; Levon Abrahamyan. Erratum to: Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus. Veterinary Research 2017, 48, 54 .

AMA Style

Chengbao Wang, Han Meng, Yujin Gao, Hui Gao, Kangkang Guo, Fernando Almazan, Isabel Sola, Luis Enjuanes, Yanming Zhang, Levon Abrahamyan. Erratum to: Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus. Veterinary Research. 2017; 48 (1):54.

Chicago/Turabian Style

Chengbao Wang; Han Meng; Yujin Gao; Hui Gao; Kangkang Guo; Fernando Almazan; Isabel Sola; Luis Enjuanes; Yanming Zhang; Levon Abrahamyan. 2017. "Erratum to: Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus." Veterinary Research 48, no. 1: 54.

Case report article
Published: 15 August 2017 in Frontiers in Microbiology
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Klebsiella pneumoniae is one of the most important infectious agents among neonates. This pathogen has a potential to develop an increased antimicrobial resistance and virulence. The classic nonvirulent strain of K. pneumoniae, producing an extended-spectrum beta-lactamases (ESBL), is associated with nosocomial infection mainly in preterm neonates. Hypervirulent K. pneumoniae strains are associated with invasive infection among previously healthy ambulatory patients, and most of them exhibit antimicrobial susceptibility. During the last few years, several cases of diseases caused by hypervirulent K. pneumoniae producing ESBL have been registered in different geographical regions of the world. However, reports of such cases in neonates are rare. Here we reported that this pathogen can cause pyogenic meningitis in full-term neonate with poor prognosis. A previously healthy, full-term, 12-day-old neonate was admitted to the infectious diseases hospital with suspected meningitis. The clinical symptoms included loss of appetite, irritability, fever, seizures, and a bulging anterior fontanelle. The analysis of the cerebrospinal fluid confirmed the diagnosis of meningitis. Blood and cerebrospinal fluid cultures were positive for K. pneumoniae, producing ESBL. K. pneumoniae isolates were resistant to aminopenicillins, 3rd generation cephalosporins but were sensitive to imipenem and meropenem. The “string test” was positive. The study of the virulence factors of K. pneumoniae by PCR revealed the presence of the rmpA gene. A combination of K. pneumoniae virulence and drug resistance complicated by cerebral oedema led to the death of the neonate. We concluded that both the risk of developing severe forms of infection and the outcome of the disease due to K. pneumonia are associated with the phenotypic features of the pathogen such as its antibiotic susceptibility and virulence factors. Emergence of the ESBL-producing strain of hypervirulent K. pneumoniae could represent a new serious threat to public health, suggesting an urgent need to enhance clinical awareness and epidemiological surveillance.

ACS Style

Khalit S. Khaertynov; Vladimir A. Anokhin; Yuri N. Davidyuk; Irina V. Nicolaeva; Svetlana V. Khalioullina; Dina R. Semyenova; Evgeny Y. Alatyrev; Natalia N. Skvortsova; Levon G. Abrahamyan. Case of Meningitis in a Neonate Caused by an Extended-Spectrum-Beta-Lactamase-Producing Strain of Hypervirulent Klebsiella pneumoniae. Frontiers in Microbiology 2017, 8, 1576 .

AMA Style

Khalit S. Khaertynov, Vladimir A. Anokhin, Yuri N. Davidyuk, Irina V. Nicolaeva, Svetlana V. Khalioullina, Dina R. Semyenova, Evgeny Y. Alatyrev, Natalia N. Skvortsova, Levon G. Abrahamyan. Case of Meningitis in a Neonate Caused by an Extended-Spectrum-Beta-Lactamase-Producing Strain of Hypervirulent Klebsiella pneumoniae. Frontiers in Microbiology. 2017; 8 ():1576.

Chicago/Turabian Style

Khalit S. Khaertynov; Vladimir A. Anokhin; Yuri N. Davidyuk; Irina V. Nicolaeva; Svetlana V. Khalioullina; Dina R. Semyenova; Evgeny Y. Alatyrev; Natalia N. Skvortsova; Levon G. Abrahamyan. 2017. "Case of Meningitis in a Neonate Caused by an Extended-Spectrum-Beta-Lactamase-Producing Strain of Hypervirulent Klebsiella pneumoniae." Frontiers in Microbiology 8, no. : 1576.

Short report
Published: 10 August 2017 in Veterinary Research
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In order to gain insight into the role of the transcription regulatory sequences (TRSs) in the regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus (PRRSV), the enhanced green fluorescent protein (EGFP) gene, under the control of the different structural gene TRSs, was inserted between the N gene and 3′-UTR of the PRRSV genome and EGFP expression was analyzed for each TRS. TRSs of all the studied structural genes of PRRSV positively modulated EGFP expression at different levels. Among the TRSs analyzed, those of GP2, GP5, M, and N genes highly enhanced EGFP expression without altering replication of PRRSV. These data indicated that structural gene TRSs could be an extremely useful tool for foreign gene expression using PRRSV as a vector.

ACS Style

Chengbao Wang; Han Meng; Yujin Gao; Hui Gao; Kangkang Guo; Fernando Almazan; Isabel Sola; Luis Enjuanes; Yanming Zhang; Levon Abrahamyan. Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus. Veterinary Research 2017, 48, 1 -7.

AMA Style

Chengbao Wang, Han Meng, Yujin Gao, Hui Gao, Kangkang Guo, Fernando Almazan, Isabel Sola, Luis Enjuanes, Yanming Zhang, Levon Abrahamyan. Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus. Veterinary Research. 2017; 48 (1):1-7.

Chicago/Turabian Style

Chengbao Wang; Han Meng; Yujin Gao; Hui Gao; Kangkang Guo; Fernando Almazan; Isabel Sola; Luis Enjuanes; Yanming Zhang; Levon Abrahamyan. 2017. "Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus." Veterinary Research 48, no. 1: 1-7.

Article
Published: 22 July 2017 in BioNanoScience
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In this paper, we report results of the study of immune parameters with the assessment of regulatory and effector subpopulations of lymphocytes and monocytes with candidiasis in children with chronic somatic diseases (secondary pyelonephritis and obstructive diseases of the upper gastrointestinal tract). Candidiasis was diagnosed by the rising level of circulating Candida albicans mannan antigen and culture mycological research. It was found that the persistence of fungi is associated with differentiated regulatory changes in the structure of subpopulations of lymphocytes and monocytes with preferential increase of immunosuppressive cells (CD4+CD25+hi, CD3+CD16/56+, CD3−CD8+, CD3+4−8−) amid reduction of effector subpopulations of lymphocytes and antigen presenting cells associated with Th1 immune response profile.

ACS Style

Elena V. Agafonova; Farida F. Rizvanova; Ayzada E. Kadyrova; Levon Abrahamyan. Regulatory Profile Changes of Lymphocytes and Peripheral Blood Monocytes in Children with Candidiasis Associated with Chronic Somatic Diseases. BioNanoScience 2017, 7, 627 -632.

AMA Style

Elena V. Agafonova, Farida F. Rizvanova, Ayzada E. Kadyrova, Levon Abrahamyan. Regulatory Profile Changes of Lymphocytes and Peripheral Blood Monocytes in Children with Candidiasis Associated with Chronic Somatic Diseases. BioNanoScience. 2017; 7 (4):627-632.

Chicago/Turabian Style

Elena V. Agafonova; Farida F. Rizvanova; Ayzada E. Kadyrova; Levon Abrahamyan. 2017. "Regulatory Profile Changes of Lymphocytes and Peripheral Blood Monocytes in Children with Candidiasis Associated with Chronic Somatic Diseases." BioNanoScience 7, no. 4: 627-632.

Original research article
Published: 16 June 2017 in Frontiers in Veterinary Science
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Bovine gammaherpesvirus 4 (BoHV-4) is a herpesvirus widespread in cattle populations, and with no clear disease association. Its genome contains a long unique coding region (LUR) flanked by polyrepetitive DNA. In 2009, a BoHV-4 strain was isolated (FMV09-1180503: BoHV-4-FMV) from cattle with respiratory disease from Quebec, Canada, and its LUR was sequenced. Despite the overall high similarity, BoHV-4-FMV had the most divergent LUR sequence compared to the two known BoHV-4 reference strain genomes; most of the divergences were in the Bo genes and in the repeat regions. Our phylogenetic analysis based on DNA polymerase and thymidine kinase genes revealed that virus isolate was BoHV-4 gammaherpesvirus and clustered it together with European BoHV-4 strains. Because BoHV-4-FMV was isolated from animals presenting respiratory signs, we have updated the BoHV-4 Canadian cattle seroprevalence data and tried to find out whether there is a link between clinical manifestation and BoHV-4 seropositivity. An indirect immunofluorescence assay (IFA) was performed with near 200 randomized sera of dairy cattle from two Canadian provinces, Quebec (n=100) and Ontario (n=91). Quebec’s sera of selected dairy cattle herds experiencing respiratory or reproductive problems (n=75) and healthy herds (n=48) were also analyzed by IFA. BoHV-4 seroprevalence in Canadian dairy cattle was 7.9% (Quebec: 6% and Ontario: 9.9%). Among Quebec’s selected herds, diseased herds showed higher BoHV-4 seropositivity than healthy herds (P<0.05), with a significant 2.494 odds ratio of being seropositive in sick compared to healthy animals. Although there is no established direct link between BoHV-4 and specific diseases, these seroprevalence data suggest the possible involvement of BoHV-4 in dairy cattle diseases.

ACS Style

Carl A. Gagnon; Carolina Kist Traesel; Nedzad Music; Jérôme Laroche; Nicolas Tison; Jean-Philippe Auger; Sanela Music; Chantale Provost; Christian Bellehumeur; Levon Abrahamyan; Susy Carman; Luc DesCôteaux; Steve J. Charette. Whole Genome Sequencing of a Canadian Bovine Gammaherpesvirus 4 Strain and the Possible Link between the Viral Infection and Respiratory and Reproductive Clinical Manifestations in Dairy Cattle. Frontiers in Veterinary Science 2017, 4, 92 -92.

AMA Style

Carl A. Gagnon, Carolina Kist Traesel, Nedzad Music, Jérôme Laroche, Nicolas Tison, Jean-Philippe Auger, Sanela Music, Chantale Provost, Christian Bellehumeur, Levon Abrahamyan, Susy Carman, Luc DesCôteaux, Steve J. Charette. Whole Genome Sequencing of a Canadian Bovine Gammaherpesvirus 4 Strain and the Possible Link between the Viral Infection and Respiratory and Reproductive Clinical Manifestations in Dairy Cattle. Frontiers in Veterinary Science. 2017; 4 ():92-92.

Chicago/Turabian Style

Carl A. Gagnon; Carolina Kist Traesel; Nedzad Music; Jérôme Laroche; Nicolas Tison; Jean-Philippe Auger; Sanela Music; Chantale Provost; Christian Bellehumeur; Levon Abrahamyan; Susy Carman; Luc DesCôteaux; Steve J. Charette. 2017. "Whole Genome Sequencing of a Canadian Bovine Gammaherpesvirus 4 Strain and the Possible Link between the Viral Infection and Respiratory and Reproductive Clinical Manifestations in Dairy Cattle." Frontiers in Veterinary Science 4, no. : 92-92.

Review
Published: 23 July 2014 in Viruses
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To get access to the replication site, small non-enveloped DNA viruses have to cross the cell membrane using a limited number of capsid proteins, which also protect the viral genome in the extracellular environment. Most of DNA viruses have to reach the nucleus to replicate. The capsid proteins involved in transmembrane penetration are exposed or released during endosomal trafficking of the virus. Subsequently, the conserved domains of capsid proteins interact with cellular membranes and ensure their efficient permeabilization. This review summarizes our current knowledge concerning the role of capsid proteins of small non-enveloped DNA viruses in intracellular membrane perturbation in the early stages of infection.

ACS Style

Eva Bilkova; Jitka Forstova; Levon Abrahamyan. Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking. Viruses 2014, 6, 2899 -2937.

AMA Style

Eva Bilkova, Jitka Forstova, Levon Abrahamyan. Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking. Viruses. 2014; 6 (7):2899-2937.

Chicago/Turabian Style

Eva Bilkova; Jitka Forstova; Levon Abrahamyan. 2014. "Coat as a Dagger: The Use of Capsid Proteins to Perforate Membranes during Non-Enveloped DNA Viruses Trafficking." Viruses 6, no. 7: 2899-2937.

Research article
Published: 23 July 2013 in PLOS ONE
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The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (“twin cysteines”) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIVcpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and ability to support virus entry. Thus, the twin-cysteine motif plays a role in Env trimer stabilization in SIV and may do so in HIV-2 and some SIVcpz as well. This implies that HIV-1 lost the twin-cysteines, and may have relatively unstable Env trimers compared to SIV and HIV-2.

ACS Style

Christopher Bohl; Dane Bowder; Jesse Thompson; Levon Abrahamyan; Sandra Gonzalez-Ramirez; Youdong Jack Mao; Joseph Sodroski; Charles Wood; Shi-Hua Xiang. A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV Envelope Trimer Stabilization. PLOS ONE 2013, 8, e69406 .

AMA Style

Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Jack Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang. A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV Envelope Trimer Stabilization. PLOS ONE. 2013; 8 (7):e69406.

Chicago/Turabian Style

Christopher Bohl; Dane Bowder; Jesse Thompson; Levon Abrahamyan; Sandra Gonzalez-Ramirez; Youdong Jack Mao; Joseph Sodroski; Charles Wood; Shi-Hua Xiang. 2013. "A Twin-Cysteine Motif in the V2 Region of gp120 Is Associated with SIV Envelope Trimer Stabilization." PLOS ONE 8, no. 7: e69406.

Research article
Published: 26 June 2013 in PLOS ONE
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A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

ACS Style

For Yue Tso; Levon Abrahamyan; Shiu-Lok Hu; Ruth M. Ruprecht; Charles Wood. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression. PLOS ONE 2013, 8, e66973 .

AMA Style

For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression. PLOS ONE. 2013; 8 (6):e66973.

Chicago/Turabian Style

For Yue Tso; Levon Abrahamyan; Shiu-Lok Hu; Ruth M. Ruprecht; Charles Wood. 2013. "Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression." PLOS ONE 8, no. 6: e66973.

Journal article
Published: 01 May 2009 in Journal of Biological Chemistry
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Our earlier work indicated that the human immunodeficiency virus type 1 (HIV-1) genomic RNA (vRNA) is trafficked to the microtubule-organizing center (MTOC) when heterogeneous nuclear ribonucleoprotein A2/B1 is depleted from cells. Also, Rab7-interacting lysosomal protein promoted dynein motor complex, late endosome and vRNA clustering at the MTOC suggesting that the dynein motor and late endosomes were involved in vRNA trafficking. To investigate the role of the dynein motor in vRNA trafficking, dynein motor function was disrupted by small interference RNA-mediated depletion of the dynein heavy chain or by p50/dynamitin overexpression. These treatments led to a marked relocalization of vRNA and viral structural protein Gag to the cell periphery with late endosomes and a severalfold increase in HIV-1 production. In contrast, rerouting vRNA to the MTOC reduced virus production. vRNA localization depended on Gag membrane association as shown using both myristoylation and Gag nucleocapsid domain proviral mutants. Furthermore, the cytoplasmic localization of vRNA and Gag was not attributable to intracellular or internalized endocytosed virus particles. Our results demonstrate that dynein motor function is important for regulating Gag and vRNA egress on endosomal membranes in the cytoplasm to directly impact on viral production.

ACS Style

Martin Lehmann; Miroslav P. Milev; Levon Abrahamyan; Xiao-Jian Yao; Nelly Pante; Andrew J. Mouland. Intracellular Transport of Human Immunodeficiency Virus Type 1 Genomic RNA and Viral Production Are Dependent on Dynein Motor Function and Late Endosome Positioning. Journal of Biological Chemistry 2009, 284, 14572 -14585.

AMA Style

Martin Lehmann, Miroslav P. Milev, Levon Abrahamyan, Xiao-Jian Yao, Nelly Pante, Andrew J. Mouland. Intracellular Transport of Human Immunodeficiency Virus Type 1 Genomic RNA and Viral Production Are Dependent on Dynein Motor Function and Late Endosome Positioning. Journal of Biological Chemistry. 2009; 284 (21):14572-14585.

Chicago/Turabian Style

Martin Lehmann; Miroslav P. Milev; Levon Abrahamyan; Xiao-Jian Yao; Nelly Pante; Andrew J. Mouland. 2009. "Intracellular Transport of Human Immunodeficiency Virus Type 1 Genomic RNA and Viral Production Are Dependent on Dynein Motor Function and Late Endosome Positioning." Journal of Biological Chemistry 284, no. 21: 14572-14585.

Journal article
Published: 05 June 2008 in Virology
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Retroviral genomic RNA (gRNA) dimerization appears essential for viral infectivity, and the nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) facilitates HIV-1 gRNA dimerization. To identify the relevant and dispensable positions of NC, 34 of its 55 residues were mutated, individually or in small groups, in a panel of 40 HIV-1 mutants prepared by site-directed mutagenesis. It was found that the amino-terminus, the proximal zinc finger, the linker, and the distal zinc finger of NC each contributed roughly equally to efficient HIV-1 gRNA dimerization. The N-terminal and linker segments appeared to play predominantly electrostatic and steric roles, respectively. Mutating the hydrophobic patch of either zinc finger, or substituting alanines for their glycine doublet, was as disabling as deleting the corresponding finger. Replacing the CysX2CysX4HisX4Cys motif of either finger by CysX2CysX4CysX4Cys or CysX2CysX4HisX4His, interchanging the zinc fingers or, replacing one zinc finger by a copy of the other one, had generally intermediate effects; among these mutations, the His23→Cys substitution in the N-terminal zinc finger had the mildest effect. The charge of NC could be increased or decreased by up to 18%, that of the linker could be reduced by 75% or increased by 50%, and one or two electric charges could be added or subtracted from either zinc finger, without affecting gRNA dimerization. Shortening, lengthening, or making hydrophobic the linker was as disabling as deleting the N-terminal or the C-terminal zinc finger, but a neutral and polar linker was innocuous. The present work multiplies by 4 and by 33 the number of retroviral and lentiviral NC mutations known to inhibit gRNA dimerization, respectively. It shows the first evidence that gRNA dimerization can be inhibited by: 1) mutations in the N-terminus or the linker of retroviral NC; 2) mutations in the proximal zinc finger of lentiviral NC; 3) mutations in the hydrophobic patch or the conserved glycines of the proximal or the distal retroviral zinc finger. Some NC mutations impaired gRNA dimerization more than mutations inactivating the viral protease, indicating that gRNA dimerization may be stimulated by the NC component of the Gag polyprotein. Most, but not all, mutations inhibited gRNA packaging; some had a strong effect on virus assembly or stability.

ACS Style

Jafar Kafaie; Rujun Song; Levon Abrahamyan; Andrew J. Mouland; Michael Laughrea. Mapping of nucleocapsid residues important for HIV-1 genomic RNA dimerization and packaging. Virology 2008, 375, 592 -610.

AMA Style

Jafar Kafaie, Rujun Song, Levon Abrahamyan, Andrew J. Mouland, Michael Laughrea. Mapping of nucleocapsid residues important for HIV-1 genomic RNA dimerization and packaging. Virology. 2008; 375 (2):592-610.

Chicago/Turabian Style

Jafar Kafaie; Rujun Song; Levon Abrahamyan; Andrew J. Mouland; Michael Laughrea. 2008. "Mapping of nucleocapsid residues important for HIV-1 genomic RNA dimerization and packaging." Virology 375, no. 2: 592-610.

Journal article
Published: 27 March 2008 in RNA
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The HIV-1 ribonucleoprotein (RNP) contains the major structural protein, pr55(Gag), viral genomic RNA, as well as the host protein, Staufen1. In this report, we show that the nonsense-mediated decay (NMD) factor UPF1 is also a component of the HIV-1 RNP. We investigated the role of UPF1 in HIV-1-expressing cells. Depletion of UPF1 by siRNA resulted in a dramatic reduction in steady-state HIV-1 RNA and pr55(Gag). Pr55(Gag) synthesis, but not the cognate genomic RNA, was efficiently rescued by expression of an siRNA-insensitive UPF1, demonstrating that UPF1 positively influences HIV-1 RNA translatability. Conversely, overexpression of UPF1 led to a dramatic up-regulation of HIV-1 expression at the RNA and protein synthesis levels. The effects of UPF1 on HIV-1 RNA stability were observed in the nucleus and cytoplasm and required ongoing translation. We also demonstrate that the effects exerted by UPF1 on HIV-1 expression were dependent on its ATPase activity, but were separable from its role in NMD and did not require interaction with UPF2.

ACS Style

L. Ajamian; L. Abrahamyan; M. Milev; P. V. Ivanov; A. E. Kulozik; N. H. Gehring; A. J. Mouland. Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation. RNA 2008, 14, 914 -927.

AMA Style

L. Ajamian, L. Abrahamyan, M. Milev, P. V. Ivanov, A. E. Kulozik, N. H. Gehring, A. J. Mouland. Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation. RNA. 2008; 14 (5):914-927.

Chicago/Turabian Style

L. Ajamian; L. Abrahamyan; M. Milev; P. V. Ivanov; A. E. Kulozik; N. H. Gehring; A. J. Mouland. 2008. "Unexpected roles for UPF1 in HIV-1 RNA metabolism and translation." RNA 14, no. 5: 914-927.

Journal article
Published: 05 March 2008 in Virology
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RNA helicases play important roles in RNA metabolism. Human immunodeficiency virus type 1 (HIV-1) does not carry its own RNA helicase, the virus thus needs to exploit cellular RNA helicases to promote the replication of its RNA at various steps such as transcription, folding and transport. In this study, we report that knockdown of a DEAD-box protein named DDX24 inhibits the packaging of HIV-1 RNA and thus diminishes viral infectivity. The decreased viral RNA packaging as a result of DDX24-knockdown is observed only in the context of the Rev/RRE (Rev response element)-dependent but not the CTE (constitutive transport element)-mediated nuclear export of viral RNA, which is explained by the specific interaction of DDX24 with the Rev protein. We propose that DDX24 acts at the early phase of HIV-1 RNA metabolism prior to nuclear export and the consequence of this action extends to the viral RNA packaging stage during virus assembly.

ACS Style

Jing Ma; Liwei Rong; Yongdong Zhou; Bibhuti Bushan Roy; Jennifer Lu; Levon Abrahamyan; Andrew J. Mouland; Qinghua Pan; Chen Liang. The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA. Virology 2008, 375, 253 -264.

AMA Style

Jing Ma, Liwei Rong, Yongdong Zhou, Bibhuti Bushan Roy, Jennifer Lu, Levon Abrahamyan, Andrew J. Mouland, Qinghua Pan, Chen Liang. The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA. Virology. 2008; 375 (1):253-264.

Chicago/Turabian Style

Jing Ma; Liwei Rong; Yongdong Zhou; Bibhuti Bushan Roy; Jennifer Lu; Levon Abrahamyan; Andrew J. Mouland; Qinghua Pan; Chen Liang. 2008. "The requirement of the DEAD-box protein DDX24 for the packaging of human immunodeficiency virus type 1 RNA." Virology 375, no. 1: 253-264.

Journal article
Published: 15 June 2007 in Journal of Virology
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Human immunodeficiency virus type 1 (HIV-1) requires the sequential activities of virus-encoded proteins during replication. The activities of several host cell proteins and machineries are also critical to the completion of virus assembly and the release of infectious virus particles from cells. One of these proteins, the double-stranded RNA-binding protein Staufen1 (Stau1), selectively associates with the HIV-1 genomic RNA and the viral precursor Gag protein, pr55 Gag . In this report, we tested whether Stau1 modulates pr55 Gag assembly using a new and specific pr55 Gag oligomerization assay based on bioluminescence resonance energy transfer (BRET) in both live cells and extracts after cell fractionation. Our results show that both the overexpression and knockdown of Stau1 increase the pr55 Gag -pr55 Gag BRET levels, suggesting a role for Stau1 in regulating pr55 Gag oligomerization during assembly. This effect of Stau1 on pr55 Gag oligomerization was observed only in membranes, a cellular compartment in which pr55 Gag assembly primarily occurs. Consistently, expression of Stau1 harboring a vSrc myristylation signal led to a 6.5-fold enrichment of Stau1 in membranes and a corresponding enhancement in the Stau1-mediated effect on pr55 Gag -pr55 Gag BRET, demonstrating that Stau1 acts on assembly when targeted to membranes. A role for Stau1 in the formation of particles is further supported by the detection of membrane-associated detergent-resistant pr55 Gag complexes and the increase of virus-like particle release when Stau1 expression levels are modulated. Our results indicate that Stau1 influences HIV-1 assembly by modulating pr55 Gag -pr55 Gag interactions, as shown in a live cell interaction assay. This likely occurs when Stau1 interacts with membrane-associated assembly intermediates.

ACS Style

Laurent Chatel-Chaix; Levon Abrahamyan; Céline Fréchina; Andrew J. Mouland; Luc DesGroseillers. The Host Protein Staufen1 Participates in Human Immunodeficiency Virus Type 1 Assembly in Live Cells by Influencing pr55 Gag Multimerization. Journal of Virology 2007, 81, 6216 -6230.

AMA Style

Laurent Chatel-Chaix, Levon Abrahamyan, Céline Fréchina, Andrew J. Mouland, Luc DesGroseillers. The Host Protein Staufen1 Participates in Human Immunodeficiency Virus Type 1 Assembly in Live Cells by Influencing pr55 Gag Multimerization. Journal of Virology. 2007; 81 (12):6216-6230.

Chicago/Turabian Style

Laurent Chatel-Chaix; Levon Abrahamyan; Céline Fréchina; Andrew J. Mouland; Luc DesGroseillers. 2007. "The Host Protein Staufen1 Participates in Human Immunodeficiency Virus Type 1 Assembly in Live Cells by Influencing pr55 Gag Multimerization." Journal of Virology 81, no. 12: 6216-6230.