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HIV and retrovirus

D Michieletto, M Lusic, D Marenduzzo, E Orlandini
Certain retroviruses, including HIV, insert their DNA in a non-random fraction of the host genome via poorly understood selection mechanisms. Here, we develop a biophysical model for retroviral integration as stochastic and quasi-equilibrium topological reconnections between polymers. We discover that physical effects, such as DNA accessibility and elasticity, play important and universal roles in this process. Our simulations predict that integration is favoured within nucleosomal and flexible DNA, in line with experiments, and that these biases arise due to competing energy barriers associated with DNA deformations...
February 4, 2019: Nature Communications
Ismael Ahmed, Seblewengel Lemma
BACKGROUND: Despite substantial improvements in accessibility of Anti-Retroviral Treatment (ART), death of children on ART remains a prevailing challenge in sub-Saharan African (SSA) countries. However, the pooled magnitude of mortality at different ART follow-up periods remains unknown for the region. We estimated the pooled proportion of all-cause mortality for pediatric patients receiving first-line ART at 3, 6, 12, and 24 months follow-up period in SSA. METHODS: We searched for relevant articles published between January 2014 and June 2018 on PubMed, Hinari and Google scholar databases...
February 4, 2019: BMC Public Health
Jennifer L Welch, Jack T Stapleton, Chioma M Okeoma
The terms extracellular vesicles, microvesicles, oncosomes, or exosomes are often used interchangeably as descriptors of particles that are released from cells and comprise a lipid membrane that encapsulates nucleic acids and proteins. Although these entities are defined based on a specific size range and/or mechanism of release, the terminology is often ambiguous. Nevertheless, these vesicles are increasingly recognized as important modulators of intercellular communication. The generic characterization of extracellular vesicles could also be used as a descriptor of enveloped viruses, highlighting the fact that extracellular vesicles and enveloped viruses are similar in both composition and function...
January 31, 2019: Journal of General Virology
Pratanporn Arirachakaran, Sureeat Luangworakhun, Georgios Charalampakis, Gunnar Dahlén
In the present study, we identified and evaluated the antibiotic susceptibility of 96 independent, aerobic, Gram-negative bacillus isolates from 255 Thai HIV-positive adults who were on Highly-active anti-retrovirus therapy (HAART) medication. Another 46 isolates from HIV non-HAART individuals, vertically transmitted HIV-positive individuals, and non-HIV controls were included for comparison. A total of 103 strains were tested for antibiotic susceptibility using disc diffusion for screening and E-test for minimal inhibitory concentration determination, with special attention on extended-spectrum beta-lactamase (ESBL) isolates...
January 30, 2019: Journal of Investigative and Clinical Dentistry
Danni Jin, Karin Musier-Forsyth
The lifecycle of retroviruses and retrotransposons includes a reverse transcription step, wherein double-stranded DNA is synthesized from their RNA genomes for subsequent insertion into the host genome. Retroviruses and retrotransposons commonly appropriate major components of the host cell translational machinery, including cellular tRNAs, which are exploited as reverse transcription primers. Non-priming functions of tRNAs have also been proposed, such as in HIV-1 virion assembly, and tRNA-derived fragments may also be involved in retrovirus and retrotransposon replication...
January 30, 2019: Journal of Biological Chemistry
Brian C Zanoni, Ryan J Elliott, Anne M Neilan, Jessica E Haberer
Introduction: Compared to adults, adolescents and young adults have a higher incidence of HIV infection, yet lower rates of HIV testing. Few evidence-based interventions effectively diagnose new HIV infections among adolescents while successfully providing linkage to care. Methods: We conducted a systematic review of recent interventions to increase HIV testing among adolescents and young adults using data retrieved from PubMed and Google Scholar, and using abstracts presented at the International AIDS Society conferences and Conference on Retroviruses and Opportunistic Infections published between January 1, 2015, and April 28, 2018...
2018: Adolescent Health, Medicine and Therapeutics
Brett D Anderson, Terumasa Ikeda, Seyed Arad Moghadasi, Amber St Martin, William L Brown, Reuben S Harris
BACKGROUND: The APOBEC3 (A3) family of DNA cytosine deaminases provides an innate barrier to infection by retroviruses including HIV-1. A total of five enzymes, A3C, A3D, A3F, A3G and A3H, are degraded by the viral accessory protein Vif and expressed at high levels in CD4+ T cells, the primary reservoir for HIV-1 replication in vivo. Apart from A3C, all of these enzymes mediate restriction of Vif-deficient HIV-1. However, a rare variant of human A3C (Ile188) was shown recently to restrict Vif-deficient HIV-1 in a 293T-based single cycle infection system...
December 17, 2018: Retrovirology
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
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