Apoptosis has been proposed as a key mechanism responsible for CD4⁺ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4⁺/CD8⁺ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4⁺ T cells, and (d) increased specific CD4⁺ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH–treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.

Background/Objectives: Enterovirus-D68 (EV-D68) and rhinoviruses are major contributors to respiratory illnesses in children, presenting a spectrum of clinical manifestations ranging from asymptomatic cases to severe lower respiratory tract infections. No specific antiviral treatments are currently approved for these viruses. Method: We conducted a comprehensive literature review of antiviral agents investigated for EV-D68 and rhinovirus infections. Results: Several antiviral candidates are under investigation, each targeting distinct stages of the viral replicative cycle. Capsid-binding agents and monoclonal antibodies prevent viral attachment by blocking receptor-virus interactions. Inhibitors of viral replication proteins disrupt polyprotein processing and replication organelle biogenesis by targeting non-structural viral proteins. Host factor inhibitors impair viral attachment, replication organelle formation, or RNA replication by interfering with critical host pathways. Conclusions: While no specific antivirals are yet approved for EV-D68 and rhinovirus infections, emerging therapeutic candidates offer potential avenues for treatment. Continued preclinical and clinical investigation will be essential to validate these approaches and expand the available options for affected patients.

Identifying immune cells and anatomical tissues that contribute to the establishment of viral reservoirs is of central importance in HIV-1 cure research. Herein, we used rhesus macaques (RMs) infected with SIVmac251 to analyze viral seeding in the liver and lungs of either untreated or early antiretroviral therapy–treated (ART-treated) RMs. Consistent with viral replication and sensing, transcriptomic analyses showed higher levels of inflammation, pyroptosis, and chemokine genes as well as of interferon-stimulating gene (ISG) transcripts, in the absence of ART. Our results highlighted the infiltration of monocyte-derived macrophages (HLA-DR ⁺ CD11b ⁺ CD14 ⁺ CD16 ⁺ ) in inflamed liver and lung tissues associated with the expression of CD183 and CX3CR1 but also with markers of tissue-resident macrophages (CD206 ⁺ and LYVE ⁺ ). Sorting of myeloid cell subsets demonstrated that CD14 ⁺ CD206 ^– , CD14 ⁺ CD206 ⁺ , and CD14 ^– CD206 ⁺ cell populations were infected, in the liver and lungs, in SIVmac251-infected RMs. Of importance, early ART drastically reduced viral seeding consistent with the absence of ISG detection but also of genes related to inflammation and tissue damage. Viral DNA was only detected in CD206 ⁺ HLA-DR ⁺ CD11b ⁺ cells in ART-treated RMs. The observation of pulmonary and hepatic viral rebound after ART interruption reinforces the importance of early ART implementation to limit viral seeding and inflammatory reactions.

Influenza virus is one of the most frequent causes of respiratory infection in humans. Recent studies suggest that extracellular vesicles (EVs)—small particles released by cells during influenza virus infection—can influence the immune response and viral pathogenesis. However, during viral replication, infected cells can also release EVs, which may include different subtypes. This study aimed to purify and characterize viral preparations and EVs using sequential ultracentrifugation methods. Influenza A/H1N1, A/H3N2, and B virus strains were produced in human Calu-3 and A549 cell lines. Viral supernatants then underwent a series of differential ultracentrifugation steps at 3000× g, 17,000× g, and 100,000× g. Dynamic light scattering analysis (DLS) validated size heterogeneity for all three types of EVs. Measurement of infectious virus particles for all three pellets showed virus enrichment at 17,000× g and 100,000× g. Dot blot analysis confirmed the enrichment of virus particles in these fractions and the presence of EV protein. This study demonstrates the presence of EVs in virus preparations and highlights the need for improved separation methods to characterize them better and explore their role in viral infection pathogenesis.

Background/Objectives: Over the last decades, our projects have been dedicated to clarifying immunopathological and virological events associated with Human Immunodeficiency Virus (HIV) infection. Methods: By using non-human primate models of pathogenic and non-pathogenic lentiviral infections, we aimed at identifying the cells and tissues in which the virus persists, despite antiretroviral therapy (ART). Indeed, the eradication of viral reservoirs is a major challenge for HIV cure. Results: We present a series of results performed in rhesus macaques of Chinese origin deciphering the virological and immunological events associated with ART that can be of interest for people living with HIV. Conclusions: This model could be of interest for understanding in whole body the clinical alteration that persist despite ART.

Plasmonic sensors are candidates for numerous clinical applications, but few examples demonstrate their performance on large sample cohorts, a necessary step for clinical translation. The COVID-19 pandemic provided an unprecedented opportunity to validate a surface plasmon resonance (SPR) sensor for SARS-CoV-2 inhibition with a cohort of over 1,000 clinical samples from the longitudinal study of a food and retail worker population. The SPR sensor provided an in vitro model to assess the level of neutralizing antibodies by measuring the inhibition of the SARS-CoV-2 spike protein interaction with ACE-2 following exposure of the spike protein to naive and immune sera (from vaccination and/or infection). In conjunction with population data on vaccination and infection, and epidemiological data from the local jurisdiction of the study cohort, it is shown that the SPR sensor performed well in assessing the level of “pseudo-neutralization” of participant sera and that the response of the SPR sensor correlates (r = 0.74) with a live virus microneutralization assay as well as with metadata of relevant events (vaccination, waves of infection, etc.) that occurred during the study period. Using these data, the article details the challenges and opportunities of using plasmonic sensors in clinical practice.