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HIV and retrovirus

Bijan Mahboubi, Christina Gavegnano, Dong-Hyun Kim, Raymond F Schinazi, Baek Kim
BACKGROUND: SAM domain and HD domain containing protein 1 (SAMHD1) is a host anti-HIV-1 restriction factor known to suppress viral reverse transcription in nondividing myeloid cells by its dNTP triphosphorylase activity that depletes cellular dNTPs. However, HIV-2 and some SIV strains rapidly replicate in macrophages due to their accessory protein, viral protein X (Vpx), which proteosomally degrades SAMHD1 and elevates dNTP levels. Endogenous reverse transcription (ERT) of retroviruses is the extra-cellular reverse transcription step that partially synthesizes proviral DNAs within cell-free viral particles before the viruses infect new cells...
October 13, 2018: Retrovirology
Jiri Vlach, Gunnar N Eastep, Ruba H Ghanam, Susan M Watanabe, Carol Carter, Jamil S Saad
For most retroviruses, including HIV-1, binding of the Gag polyprotein to the plasma membrane (PM) is mediated by interactions between Gag's N-terminal myristoylated matrix (MA) domain and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the PM. The Gag protein of avian sarcoma virus (ASV) lacks the N-myristoylation signal but contains structural domains having functions similar to those of HIV-1 Gag. The molecular mechanism by which ASV Gag binds to the PM is incompletely understood. Here, we employed NMR techniques to elucidate the molecular determinants of the membrane-binding domain of ASV MA (MA87) to lipids and liposomes...
October 11, 2018: Journal of Biological Chemistry
Jonathan M O Rawson, Olga A Nikolaitchik, Brandon F Keele, Vinay K Pathak, Wei-Shau Hu
Retroviruses package two complete RNA genomes into a viral particle but generate only one provirus after each infection. This pseudodiploid replication strategy facilitates frequent recombination, which occurs during DNA synthesis when reverse transcriptase switches templates between two copackaged RNA genomes, generating chimeric DNA. Recombination has played an important role in shaping the current HIV-1 pandemic; however, whether recombination is required for HIV-1 replication is currently unknown. In this report, we examined viral replication when recombination was blocked in defined regions of the HIV-1 genome...
October 11, 2018: Nucleic Acids Research
Diako Ebrahimi, Christopher M Richards, Michael A Carpenter, Jiayi Wang, Terumasa Ikeda, Jordan T Becker, Adam Z Cheng, Jennifer L McCann, Nadine M Shaban, Daniel J Salamango, Gabriel J Starrett, Jairam R Lingappa, Jeongsik Yong, William L Brown, Reuben S Harris
Human APOBEC3H (A3H) is a single-stranded DNA cytosine deaminase that inhibits HIV-1. Seven haplotypes (I-VII) and four splice variants (SV154/182/183/200) with differing antiviral activities and geographic distributions have been described, but the genetic and mechanistic basis for variant expression and function remains unclear. Using a combined bioinformatic/experimental analysis, we find that SV200 expression is specific to haplotype II, which is primarily found in sub-Saharan Africa. The underlying genetic mechanism for differential mRNA splicing is an ancient intronic deletion [del(ctc)] within A3H haplotype II sequence...
October 8, 2018: Nature Communications
Claudia Firrito, Cinzia Bertelli, Teresa Vanzo, Ajit Chande, Massimo Pizzato
SERINC genes encode for homologous multipass transmembrane proteins with unknown cellular function, despite being highly conserved across eukaryotes. Among the five SERINC genes found in humans, SERINC5 was shown to act as a powerful inhibitor of retroviruses. It is efficiently incorporated into virions and blocks the penetration of the viral core into target cells, by impairing the fusion process with a yet unclear mechanism. SERINC5 was also found to promote human immunodeficiency virus 1 (HIV-1) virion neutralization by antibodies, indicating a pleiotropic activity, which remains mostly unexplored...
September 29, 2018: Annual Review of Virology
Timokratis Karamitros, Tara Hurst, Emanuele Marchi, Eirini Karamichali, Urania Georgopoulou, Andreas Mentis, Joey Riepsaame, Audrey Lin, Dimitrios Paraskevis, Angelos Hatzakis, John McLauchlan, Aris Katzourakis, Gkikas Magiorkinis
HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2 , a gene that affects dopaminergic activity and is thus related to addiction. Here we show that this antisense HK2 integration (namely RASGRF2-int) is found more frequently in persons who inject drugs compared with the general population...
October 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mohsen Keshavarz, Mohammad Hadi Karbalaie Niya, Fahimeh Safarnezhad Tameshkel, Amir Sasan Mozaffari Nejad, Seyed Hamidreza Monavari, Hossein Keyvani
Background: Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus, which has been detected in patients with prostate cancer, chronic fatigue syndrome, and general population with a number of acquired infections such as infection with human T-cell lymphotropic virus (HTLV) and human immunodeficiency virus (HIV). The aim of this study was to determine the HTLV-1 and XMRV coinfection for the first time in Iranian patients who were admitted to the Tehran hospitals. Materials and Methods: Two hundred and ninety one patients suspected with HTLV-1 were referred to the hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran from April 2012 to October 2016...
July 2018: Journal of Pharmacy & Bioallied Sciences
Weixin Wu, Joshua Hatterschide, Yu-Ci Syu, William A Cantara, Ruth J Blower, Heather M Hanson, Louis M Mansky, Karin Musier-Forsyth
Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role...
September 14, 2018: Journal of Biological Chemistry
Sibes Bera, Krishan K Pandey, Hideki Aihara, Duane P Grandgenett
Retrovirus integrase (IN) catalyzes the concerted integration of linear viral DNA ends into chromosomes. The atomic structures of five different retrovirus IN-DNA complexes, termed intasomes, have revealed varying IN subunit compositions ranging from tetramers to octamers, dodecamers, and hexadecamers. Intasomes containing two IN-associated viral DNA ends capable of concerted integration are termed stable synaptic complexes (SSC), whereas those formed with a viral/target DNA substrate representing the product of strand-transfer reactions are strand-transfer complexes (STC)...
September 5, 2018: Journal of Biological Chemistry
John P Eichorst, Yan Chen, Joachim D Mueller, Louis M Mansky
The assembly of virus particles is a crucial aspect of virus spread. For retroviruses, the Gag polyprotein is the key driver for virus particle assembly. In order to produce progeny virus, once Gag is translated, it must translocate from the location in the cytoplasm where it is synthesized to the plasma membrane and form an oligomeric lattice that results in Gag puncta. The biogenesis of mature Gag puncta can trigger the budding process, resulting in virus particle production. While some aspects of the dynamics of Gag oligomerization and particle biogenesis have been observed with human immunodeficiency virus type 1 (HIV-1), the process of Gag punctum biogenesis remains poorly understood, particularly for other retroviruses...
September 4, 2018: MBio
Celina Abreu, Erin N Shirk, Suzanne E Queen, Joseph L Mankowski, Lucio Gama, Janice E Clements
Lentiviruses are retroviruses that primarily infect myeloid cells, leading to acute inflammatory infections in many tissues particularly, lung, joints and the central nervous system (CNS). Acute infection by lentiviruses is followed by persistent/latent infections that are not cleared by the host immune system. HIV and SIV are lentiviruses that also infect CD4+ lymphocytes as well as myeloid cells in blood and multiple tissues. HIV infection of myeloid cells in brain, lung and heart cause tissue specific diseases as well as infect cells in gut, lymph nodes and spleen...
August 30, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Mvr Ratnam, Abhishek Singh Nayyar, D Santhosh Reddy, B Ruparani, K V Chalapathi, Sania Md Azmi
Context: Acquired immunodeficiency syndrome (AIDS) is an acronym for AIDS caused by a retrovirus known as human immunodeficiency virus (HIV) which breaks down the body's immune system leaving a patient vulnerable to a host of life-threatening opportunistic infections, neurological disorders or unusual malignancies. According to estimates by the World Health Organization and UNAIDS, 35 million people were living with HIV globally at the end of 2013. The first AIDS case in India was detected in 1986...
May 2018: Journal of Oral and Maxillofacial Pathology: JOMFP
Shilpi Sharma, Mary K Lewinski, John Guatelli
SERINC5 is an inhibitor of retroviral infectivity that is counteracted by viral proteins, including HIV-1 Nef. Inhibition of infectivity by SERINC5 is associated with its incorporation into virions. Nef counteracts this inhibition, presumably by removing SERINC5 from sites of virion assembly at the plasma membrane. While evaluating the virion-incorporation of SERINC5, we observed that a relatively high molecular weight form was preferentially present in virions. We used various glycosidases to establish that virion-associated SERINC5 is modified by N-linked, complex glycans, whereas the majority of SERINC5 in cells is of relatively low molecular weight and is modified by high-mannose glycans...
August 29, 2018: Journal of Virology
Daniela A Covino, Cristina Purificato, Laura Catapano, Clementina M Galluzzo, Maria Cristina Gauzzi, Stefano Vella, Eric Lefebvre, Star Seyedkazemi, Mauro Andreotti, Laura Fantuzzi
Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro . However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up...
2018: Frontiers in Immunology
Rajendra Singh, Charlotte Stoneham, Christopher Lim, Xiaofei Jia, Javier Guenaga, Richard Wyatt, Joel O Wertheim, Yong Xiong, John Guatelli
Protein trafficking in the endosomal system involves the recognition of specific signals within the cytoplasmic domains (CDs) of transmembrane proteins by clathrin adaptors. One such signal is the phosphoserine acidic cluster (PSAC), the prototype of which is in the endoprotease furin. How PSACs are recognized by clathrin adaptors has been controversial. We reported previously that HIV-1 Vpu, which modulates cellular immunoreceptors, contains a PSAC that binds to the μ subunits of clathrin adaptor protein (AP) complexes...
October 5, 2018: Journal of Biological Chemistry
Samantha Barichievy, Jerolen Naidoo, Mikaël Boullé, Janine Scholefield, Suraj P Parihar, Anna K Coussens, Frank Brombacher, Alex Sigal, Musa M Mhlanga
An emerging realization of infectious disease is that pathogens can cause a high incidence of genetic instability within the host as a result of infection-induced DNA lesions. These often lead to classical hallmarks of cancer, one of which is the ability to evade apoptosis despite the presence of numerous genetic mutations that should be otherwise lethal. The Human Immunodeficiency Virus type 1 (HIV-1) is one such pathogen as it induces apoptosis in CD4+ T cells but is largely non-cytopathic in macrophages...
2018: Frontiers in Cellular and Infection Microbiology
Jingyou Yu, Shan-Lu Liu
Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4⁺ T cells and monocytes/macrophages has not been investigated in detail...
August 7, 2018: Viruses
Kristina Meier, Ananda Ayyappan Jaguva Vasudevan, Zeli Zhang, Ariane Bähr, Georg Kochs, Dieter Häussinger, Carsten Münk
Human myxovirus resistance protein B (hMXB) is a restriction factor of HIV-1 that also inhibits a variety of retroviruses. However, hMXB is not antiviral against equine infectious anemia virus (EIAV). We show here that equine MX2 (eMX2) potently restricts EIAV in vitro. Additionally, eMX2 inhibits HIV-1 and other lentiviruses, including murine leukemia virus. Previously, it was reported that hMXB repression is reduced in hMXB Δ1-25, but not in GTP-binding mutant K131A and GTP-hydrolysis mutant T151A. In contrast to this phenomenon, our study indicates that eMX2 restriction is not diminished in eMX2 Δ1-25, but is in eMX2 K127A and T147A, which correspond to hMXB K131A and T151A, respectively...
October 2018: Virology
Kunchok Dorjee, Tsering Choden, Sanjiv M Baxi, Craig Steinmaus, Arthur L Reingold
OBJECTIVES: Abacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure. METHODS: We searched Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, and International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH...
July 21, 2018: International Journal of Antimicrobial Agents
Ingrid Eshun-Wilson, Mbah P Okwen, Marty Richardson, Tihana Bicanic
BACKGROUND: There remains uncertainty about the optimum timing of antiretroviral therapy (ART) initiation in HIV-positive people with cryptococcal meningitis. This uncertainty is the result of conflicting data on the mortality risk and occurrence of immune reconstitution inflammatory syndrome (IRIS) when ART is initiated less than four weeks after cryptococcal meningitis treatment is commenced. OBJECTIVES: To compare the outcomes of early initiation of ART (less than four weeks after starting antifungal treatment) versus delayed initiation of ART (four weeks or more after starting antifungal treatment) in HIV-positive people with concurrent cryptococcal meningitis...
July 24, 2018: Cochrane Database of Systematic Reviews
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