9,232 results match your criteria simian immunodeficiency


Ultrasensitive detection and quantification of viral nucleic acids with raindance droplet digital PCR (ddPCR).

Methods 2021 May 3. Epub 2021 May 3.

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States.

Sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by SARS-CoV2, HIV-1, and other viruses. In HIV-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cART) has benefited tremendously from the development of sensitive HIV-1 DNA and RNA quantitation assays. Simian immunodeficiency virus (SIV) infection of Rhesus macaques is similar in many key aspects to human HIV-1 infection and consequently this non-human primate (NHP) model has and continues to prove instrumental in evaluating HIV prevention, treatment and eradication approaches. Read More

View Article and Full-Text PDF

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques.

Cells 2021 Apr 4;10(4). Epub 2021 Apr 4.

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA.

Transforming growth factor-β signaling (TGF-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-β promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-β production that attributes to its pathological manifestations remain unknown. Read More

View Article and Full-Text PDF

Recombinant Herpesvirus Vectors: Durable Immune Responses and Durable Protection Against SIVmac239 Acquisition.

J Virol 2021 Apr 28. Epub 2021 Apr 28.

Department of Immunology and Microbiology, Scripps Research, Jupiter, Florida, USA.

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. Read More

View Article and Full-Text PDF

HIV/SIV-infection induces opening of Pannexin-1 channels resulting in neuronal synaptic compromise: a novel therapeutic opportunity to prevent NeuroHIV.

J Neurochem 2021 Apr 26. Epub 2021 Apr 26.

Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.

In healthy conditions, pannexin-1 (Panx-1) channels are in a close state, but in several pathological conditions, including HIV and NeuroHIV, the channel becomes open. However, the mechanism or contribution of Panx-1 channels to the Human Immunodeficiency Virus-1 (HIV) pathogenesis and NeuroHIV are unknown. To determine the contribution of Panx-1 channels to the pathogenesis of NeuroHIV, we used a well-established model of Simian Immunodeficiency Virus (SIV) infection in macaques (Macaca mulatta) in the presence of and absence of a Panx-1 blocker to later examine the synaptic/axonal compromise induced for the virus. Read More

View Article and Full-Text PDF

Role of NKG2a/cCD8 T cells in pathogenic versus non-pathogenic SIV infections.

iScience 2021 Apr 15;24(4):102314. Epub 2021 Mar 15.

Institut Pasteur, Unité HIV, Inflammation et Persistance, 28 rue du Dr Roux, Paris 75015, France.

Some viruses have established an equilibrium with their host. African green monkeys (AGM) display persistent high viral replication in the blood and intestine during Simian immunodeficiency virus (SIV) infection but resolve systemic inflammation after acute infection and lack intestinal immune or tissue damage during chronic infection. We show that NKG2CD8 T cells increase in the blood and intestine of AGM in response to SIVagm infection in contrast to SIVmac infection in macaques, the latter modeling HIV infection. Read More

View Article and Full-Text PDF

FRugally Optimized DNA Octomer (FRODO) qPCR Measurement of HIV and SIV in Human and Nonhuman Primate Samples.

Curr Protoc 2021 Apr;1(4):e93

Barrier Immunity Section, Laboratory of Viral Diseases, National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland.

Quantitative polymerase chain reactions (qPCRs) are commonly employed to enumerate genes of interest among particular biological samples. Insertion of PCR amplicons into plasmid DNA is a mainstay for creation of known quantities of target sequences to standardize qPCRs. Typically, one amplicon is inserted into one plasmid construct, and the plasmid is then amplified, purified, serially diluted, and quantified to be used to enumerate target sequences in unknown samples. Read More

View Article and Full-Text PDF

Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus.

Emerg Microbes Infect 2021 Dec;10(1):810-821

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

EK1 peptide is a membrane fusion inhibitor with broad-spectrum activity against human coronaviruses (CoVs). In the outbreak of COVID-19, we generated a lipopeptide EK1V1 by modifying EK1 with cholesterol, which exhibited significantly improved antiviral activity. In this study, we surprisingly found that EK1V1 also displayed potent cross-inhibitory activities against divergent HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates. Read More

View Article and Full-Text PDF
December 2021

Gut Microbiome Homeostasis and the CD4 T- Follicular Helper Cell IgA Axis in Human Immunodeficiency Virus Infection.

Front Immunol 2021 19;12:657679. Epub 2021 Mar 19.

F. E. Hebert School of Medicine, Uniformed Services University, Bethesda, MD, United States.

Human Immunodeficiency Virus (HIV) and Simian Immunodeficiency Virus (SIV) are associated with severe perturbations in the gut mucosal environment characterized by massive viral replication and depletion of CD4 T cells leading to dysbiosis, breakdown of the epithelial barrier, microbial translocation, immune activation and disease progression. Multiple mechanisms play a role in maintaining homeostasis in the gut mucosa and protecting the integrity of the epithelial barrier. Among these are the secretory IgA (sIgA) that are produced daily in vast quantities throughout the mucosa and play a pivotal role in preventing commensal microbes from breaching the epithelial barrier. Read More

View Article and Full-Text PDF

ART administration reduces neuroinflammation without restoring BDNF signaling in alcohol-administered SIV-infected macaques.

AIDS 2021 Mar 31. Epub 2021 Mar 31.

Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, LA Department of Microbiology, Immunology, and Parasitology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA Biostatistics, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA.

Objective: This study examined interactions between simian immunodeficiency virus (SIV), chronic binge alcohol (CBA), and antiretroviral therapy (ART) on growth factor signaling, neuroinflammatory markers, viral loads (VL), and CD4 counts.

Design: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week) or sucrose (SUC) three months prior to SIVmac251 infection until study endpoint. At viral setpoint, a subset of CBA/SIV+ and SUC/SIV+ macaques were randomized to receive daily ART (PMPA 20 mg/kg, FTC, 30 mg/kg). Read More

View Article and Full-Text PDF

Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection.

Antioxidants (Basel) 2021 Mar 9;10(3). Epub 2021 Mar 9.

Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8-T-lymphocyte-depleted rhesus macaques were studied. Read More

View Article and Full-Text PDF

Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages.

Viruses 2021 03 2;13(3). Epub 2021 Mar 2.

Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa.

Rhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo passage. SHIV recovered from the peripheral blood of the final ChRM was used to generate a ChRM-adapted virus challenge stock. Read More

View Article and Full-Text PDF

Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques.

Front Immunol 2021 16;12:657424. Epub 2021 Mar 16.

Department of Pathology, George Washington University, Washington, DC, United States.

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with , , and , as part of a previous study conducted by our group. Read More

View Article and Full-Text PDF

Improved Detection of HIV Gag p24 Protein Using a Combined Immunoprecipitation and Digital ELISA Method.

Front Microbiol 2021 16;12:636703. Epub 2021 Mar 16.

Department of Infectious Disease and Vaccines, Merck & Co. Inc., Kenilworth, NJ, United States.

Greater than 90% of HIV-1 proviruses are thought to be defective and incapable of viral replication. While replication competent proviruses are of primary concern with respect to disease progression or transmission, studies have shown that even defective proviruses are not silent and can produce viral proteins, which may contribute to inflammation and immune responses. Viral protein expression also has implications for immune-based HIV-1 clearance strategies, which rely on antigen recognition. Read More

View Article and Full-Text PDF

Chronic Opioid Administration is Associated with Prevotella-dominated Dysbiosis in SIVmac251 Infected, cART-treated Macaques.

J Neuroimmune Pharmacol 2021 Mar 31. Epub 2021 Mar 31.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

People living with the human immunodeficiency virus (HIV) have an elevated risk of opioid misuse due to both prescriptions for HIV-associated chronic pain and because injection drug use remains a primary mode of HIV transmission. HIV pathogenesis is characterized by chronic immune activation and microbial dysbiosis, and translocation across the gut barrier exacerbating inflammation. Despite the high rate of co-occurrence, little is known about the microbiome during chronic opioid use in the context of HIV and combination antiretroviral therapy (cART). Read More

View Article and Full-Text PDF

Synergy and allostery in ligand binding by HIV-1 Nef.

Biochem J 2021 Apr;478(8):1525-1545

King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Biological and Environmental Science and Engineering (BESE), Thuwal 23955-6900, Saudi Arabia.

The Nef protein of human and simian immunodeficiency viruses boosts viral pathogenicity through its interactions with host cell proteins. By combining the polyvalency of its large unstructured regions with the binding selectivity and strength of its folded core domain, Nef can associate with many different host cell proteins, thereby disrupting their functions. For example, the combination of a linear proline-rich motif and hydrophobic core domain surface allows Nef to bind tightly and specifically to SH3 domains of Src family kinases. Read More

View Article and Full-Text PDF

Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, RT-SHIV RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates.

Antimicrob Agents Chemother 2021 Mar 29. Epub 2021 Mar 29.

Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

HIV persistence in tissue reservoirs is a major barrier to HIV cure. While antiretrovirals (ARVs) suppress viral replication, antiretroviral therapy (ART) interruption results in rapid rebound viremia that may originate from lymphoid tissues. To understand the relationship between anatomic distribution of ARV exposure and viral expression in lymph nodes, we performed mass spectrometry imaging (MSI) of 6 ARVs, RNAscope hybridization for viral RNA, and immunohistochemistry of collagen in mesenteric lymph nodes from 8 uninfected and 10 reverse transcriptase-simian/human immunodeficiency virus (RT-SHIV) infected rhesus macaque nonhuman primates (NHPs) dosed to steady-state with combination ART. Read More

View Article and Full-Text PDF

CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Lukuru Wildlife Research Foundation, Tshuapa-Lomami-Lualaba Project, BP 2012, Kinshasa, Democratic Republic of the Congo.

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Read More

View Article and Full-Text PDF

Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy.

Science 2021 04 25;372(6541). Epub 2021 Mar 25.

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.

Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8 T cells recognizing epitopes presented by major histocompatibility complex II (MHC-II) and MHC-E but not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular MHC-E transport and recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8 T cells. Read More

View Article and Full-Text PDF

Cytomegaloviral determinants of CD8 T cell programming and RhCMV/SIV vaccine efficacy.

Sci Immunol 2021 Mar;6(57)

Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.

Simian immunodeficiency virus (SIV) insert-expressing, 68-1 rhesus cytomegalovirus (RhCMV/SIV) vectors elicit major histocompatibility complex E (MHC-E)- and MHC-II-restricted, SIV-specific CD8 T cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against SIV challenge in the rhesus monkeys (RMs) have not been characterized. We show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 RhCMV that abrogated the function of eight distinct immunomodulatory gene products encoded in two RhCMV genomic regions ( and ), revealing three patterns of unconventional response inhibition. Differential repair of these genes with either RhCMV-derived or orthologous human CMV (HCMV)-derived sequences (; ) leads to either of two distinct CD8 T cell response types-MHC-Ia-restricted only or a mix of MHC-II- and MHC-Ia-restricted CD8 T cells. Read More

View Article and Full-Text PDF

HLA-E-restricted, Gag-specific CD8 T cells can suppress HIV-1 infection, offering vaccine opportunities.

Sci Immunol 2021 Mar;6(57)

NDM Research Building, Nuffield Department of Medicine, Oxford University, Oxford OX3 7FZ, UK.

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Read More

View Article and Full-Text PDF

Luminal microvesicles uniquely influence translocating bacteria after SIV infection.

Mucosal Immunol 2021 Mar 17. Epub 2021 Mar 17.

Barrier Immunity Section, Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Microbial translocation contributes to persistent inflammation in both treated and untreated HIV infection. Although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of Proteobacteria. We hypothesized that intestinal epithelial microvesicle cargo differs after HIV infection and contributes to biased translocation. Read More

View Article and Full-Text PDF

Significant higher-level C-C motif chemokine ligand 2/3 and chemotactic power in cerebral white matter than grey matter in rat and human.

Eur J Neurosci 2021 Mar 16. Epub 2021 Mar 16.

Department of Pharmacology and Experiment Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.

Recent observations indicate that cerebral white matter (WM) exhibits a higher chemoattractant capability for immune cells. The C-C motif chemokine ligands 2 and 3 (CCL2, CCL3) are key chemokines for monocytes and T cells. However, tissue differential of these chemokines is unclear, although the higher CCL2/3 mRNA levels were found in rodent WM. Read More

View Article and Full-Text PDF

Modeling the Effects of Latency Reversing Drugs During HIV-1 and SIV Brain Infection with Implications for the "Shock and Kill" Strategy.

Bull Math Biol 2021 Mar 12;83(4):39. Epub 2021 Mar 12.

Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB, T6G 2G1, Canada.

Combination antiretroviral therapy (cART) has greatly increased life expectancy for human immunodeficiency virus-1 (HIV-1)-infected patients. Even given the remarkable success of cART, the virus persists in many different cells and tissues. The presence of viral reservoirs represents a major obstacle to HIV-1 eradication. Read More

View Article and Full-Text PDF

Comparison of predictors for terminal disease progression in simian immunodeficiency virus/simian-HIV-infected rhesus macaques.

AIDS 2021 Jun;35(7):1021-1029

Division of Immunology, Tulane National Primate Research Center, Covington, Louisiana.

Objectives: CD4+ T-cell decline and increasing virus levels are considered hallmarks of HIV/AIDS pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by simian immunodeficiency virus (SIV) infection associated with increased monocyte turnover also appear to impact pathogenesis. It remains unclear, however, which factors best predict onset of terminal disease progression and survival time. The objective of this study, therefore, was to directly compare these co-variates of infection for predicting survival times in retrospective studies of SIV/simian-HIV (SHIV)-infected adult rhesus macaques. Read More

View Article and Full-Text PDF

Two Human Monoclonal HLA-Reactive Antibodies Cross-React with Mamu-B*008, a Rhesus Macaque MHC Allotype Associated with Control of Simian Immunodeficiency Virus Replication.

J Immunol 2021 Apr 10;206(8):1957-1965. Epub 2021 Mar 10.

Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.

MHC class I molecules play an important role in adaptive immune responses against intracellular pathogens. These molecules are highly polymorphic, and many allotypes have been characterized. In a transplantation setting, a mismatch between MHC allotypes may initiate an alloimmune response. Read More

View Article and Full-Text PDF

Persistence of viral RNA in lymph nodes in ART-suppressed SIV/SHIV-infected Rhesus Macaques.

Nat Commun 2021 03 5;12(1):1474. Epub 2021 Mar 5.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

The establishment of a long-lived viral reservoir is the key obstacle for achieving an HIV-1 cure. However, the anatomic, virologic, and immunologic features of the viral reservoir in tissues during antiretroviral therapy (ART) remain poorly understood. Here we present a comprehensive necroscopic analysis of the SIV/SHIV viral reservoir in multiple lymphoid and non-lymphoid tissues from SIV/SHIV-infected rhesus macaques suppressed with ART for one year. Read More

View Article and Full-Text PDF

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention and Cure.

J Virol 2021 Mar 3. Epub 2021 Mar 3.

Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Previously, we showed that substitution of HIV-1 Env residue 375-Ser by bulky aromatic residues enhances binding to rhesus CD4 and enables primary HIV-1 Envs to support efficient replication as simian-human immunodeficiency virus (SHIV) chimeras in rhesus macaques (RMs). Here, we test this design strategy more broadly by constructing SHIVs containing ten primary Envs corresponding to HIV-1 subtypes A, B, C, AE and AG. All ten SHIVs bearing wildtype Env375 residues replicated efficiently in human CD4 T cells, but only one replicated efficiently in primary rhesus cells. Read More

View Article and Full-Text PDF

An Evidence for a Novel Antiviral Mechanism: Modulating Effects of Arg-Glc Maillard Reaction Products on the Phase Transition of Multilamellar Vesicles.

Front Cell Dev Biol 2020 28;8:629775. Epub 2021 Jan 28.

Food Nutrition Sciences Centre, Zhejiang Gongshang University, Hangzhou, China.

Maillard reaction products (MRPs) of protein, amino acids, and reducing sugars from many foods and aqueous extracts of herbs are found to have various bioactivities, including antiviral effects. A hypothesis was proposed that their antiviral activity is due to the interaction with the cellular membrane. Aiming to estimate the possible actions of MRPs on phospholipid bilayers, the Arg-Glc MRPs were prepared by boiling the pre-mixed solution of arginine and glucose for 60 min at 100°C and then examined at a series of concentrations for their effects on the phase transition of MeDOPE multilamellar vesicles (MLVs), for the first time, by using differential scanning calorimetry (DSC) and temperature-resolved small-angle X-ray scattering (SAXS). Read More

View Article and Full-Text PDF
January 2021

SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity.

Nat Commun 2021 02 24;12(1):1282. Epub 2021 Feb 24.

Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France.

Natural killer (NK) cells play a critical understudied role during HIV infection in tissues. In a natural host of SIV, the African green monkey (AGM), NK cells mediate a strong control of SIVagm infection in secondary lymphoid tissues. We demonstrate that SIVagm infection induces the expansion of terminally differentiated NKG2a NK cells in secondary lymphoid organs displaying an adaptive transcriptional profile and increased MHC-E-restricted cytotoxicity in response to SIV Env peptides while expressing little IFN-γ. Read More

View Article and Full-Text PDF
February 2021

HIV-1 Nef-Induced Secretion of the Proinflammatory Protease TACE into Extracellular Vesicles Is Mediated by Raf-1 and Can Be Suppressed by Clinical Protein Kinase Inhibitors.

J Virol 2021 04 12;95(9). Epub 2021 Apr 12.

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Chronic immune activation is an important driver of human immunodeficiency virus type 1 (HIV-1) pathogenesis and has been associated with the presence of tumor necrosis factor-α converting enzyme (TACE) in extracellular vesicles (EVs) circulating in infected individuals. We have recently shown that activation of the Src-family tyrosine kinase hematopoietic cell kinase (Hck) by HIV-1 Nef can trigger the packaging of TACE into EVs via an unconventional protein secretion pathway. Using a panel of HIV-1 Nef mutants and natural HIV-2 and simian immunodeficiency virus (SIV) Nef alleles, we now show that the capacity to promote TACE secretion depends on the superior ability of HIV-1-like Nef alleles to induce Hck kinase activity, whereas other Nef effector functions are dispensable. Read More

View Article and Full-Text PDF