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HIV and retrovirus

Guru KrishnaKumar Viswanathan, Satabdee Mohapatra, Ashim Paul, Elad Arad, Raz Jelinek, Ehud Gazit, Daniel Segal
PAP248⁻286 , a 39 amino acid peptide fragment, derived from the prostatic acid phosphatase secreted in human semen, forms amyloid fibrils and facilitates the attachment of retroviruses to host cells that results in the enhancement of viral infection. Therefore, the inhibition of amyloid formation by PAP248⁻286 (termed PAP f39) may likely reduce HIV transmission in AIDS. In this study, we show that the naphthoquinone tryptophan (NQTrp) hybrid molecule significantly inhibited PAP f39 aggregation in vitro in a dose-dependent manner as observed from the ThT assay, ANS assay, and transmission electron microscopy imaging...
December 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Keiko Yasuma-Mitobe, Masao Matsuoka
Costimulatory and coinhibitory receptors play a key role in regulating immune responses to infection and cancer. Coinhibitory receptors include programmed cell death 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T cell immunoglobulin and ITIM domain (TIGIT), which suppress immune responses. Coinhibitory receptors are highly expressed on exhausted virus-specific T cells, indicating that viruses evade host immune responses through enhanced expression of these molecules. Human retroviruses, human immunodeficiency virus (HIV) and human T-cell leukemia virus type 1 (HTLV-1), infect T cells, macrophages and dendritic cells...
2018: Frontiers in Immunology
Kun Qu, Bärbel Glass, Michal Doležal, Florian K M Schur, Brice Murciano, Alan Rein, Michaela Rumlová, Tomáš Ruml, Hans-Georg Kräusslich, John A G Briggs
Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical γ-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown...
November 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sunan Li, Iqbal Ahmad, Jing Shi, Bin Wang, Changqing Yu, Lixin Zhang, Yong-Hui Zheng
Glycosylated Gag (glycoGag) is an accessory protein expressed by most gamma-retroviruses including murine leukemia virus (MLV). MLV glycoGag not only enhances MLV replication and disease progression but also increases human immunodeficiency virus type 1 (HIV-1) infectivity as Nef does. Recently, SERINC5 (Ser5) was identified as the target for Nef, and the glycoGag Nef-like activity has been attributed to the Ser5 antagonism. Here, we investigated how glycoGag antagonizes Ser5 using MLV glycoMA and murine Ser5 proteins...
October 24, 2018: Journal of Virology
Elizabeth M Anderson, Frank Maldarelli
Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells...
October 23, 2018: Retrovirology
Abdullah Ebrahim Laher, Osman Ebrahim
HIV and HTLV (Human T-ymphotropic Virus) are the only known retroviruses responsible for causing infection in humans. HTLV-1 and HIV-1 are frequent co-pathogens, however, despite its potential for accelerated progression of HIV disease and the risk of developing adult T-cell lymphoma/leukemia (ATLL), HTLV-1 is seldom considered for investigation in the HIV-1 positive individual. Severe/refractory hypercalcaemia, unresponsive to conventional calcium lowering therapy may complicate up to 70% of cases of ATLL...
2018: Pan African Medical Journal
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...
November 16, 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...
October 19, 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), and those formed with a viral/target DNA substrate representing the product of strand-transfer reactions are strand-transfer complexes (STC)...
October 19, 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...
November 15, 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
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