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HIV viral dynamics

Eileen P Scully
PURPOSE OF REVIEW: This review will outline the multilevel effects of biological sex on HIV acquisition, pathogenesis, treatment response, and prospects for cure. Potential mechanisms will be discussed along with future research directions. RECENT FINDINGS: HIV acquisition risk is modified by sex hormones and the vaginal microbiome, with the latter acting through both inflammation and local metabolism of pre-exposure prophylaxis drugs. Female sex associates with enhanced risk for non-AIDS morbidities including cardiovascular and cerebrovascular disease, suggesting different inflammatory profiles in men and women...
March 5, 2018: Current HIV/AIDS Reports
Victoria Oakes, Johana Torralba, Edurne Rujas, José L Nieva, Carmen Domene, Beatriz Apellaniz
The 10E8 antibody achieves near-pan neutralization of HIV-1 by targeting the remarkably conserved gp41 membrane-proximal external region (MPER) and the connected transmembrane domain (TMD) of the HIV-1 envelope glycoprotein (Env). Thus, recreating the structure that generates 10E8-like antibodies is a major goal of the rational design of anti-HIV vaccines. Unfortunately, high-resolution information of this segment in the native Env is lacking, limiting our understanding of the behavior of the crucial 10E8 epitope residues...
February 22, 2018: Biochimica et Biophysica Acta
Cameron J Browne, Hal L Smith
The host immune response can often efficiently suppress a virus infection, which may lead to selection for immune-resistant viral variants within the host. For example, during HIV infection, an array of CTL immune response populations recognize specific epitopes (viral proteins) presented on the surface of infected cells to effectively mediate their killing. However HIV can rapidly evolve resistance to CTL attack at different epitopes, inducing a dynamic network of interacting viral and immune response variants...
February 23, 2018: Journal of Mathematical Biology
Romina Quercia, Carlo-Federico Perno, Justin Koteff, Katy Moore, Cynthia McCoig, Marty St Clair, Daniel Kuritzkes
Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease...
February 22, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Yiding Yang, Vitaly V Ganusov
Cytotoxic T lymphocytes (CTLs) have been suggested to play an important role in controlling human immunodeficiency virus (HIV-1 or simply HIV) infection. HIV, due to its high mutation rate, can evade recognition of T cell responses by generating escape variants that cannot be recognized by HIV-specific CTLs. Although HIV escape from CTL responses has been well documented, factors contributing to the timing and the rate of viral escape from T cells have not been fully elucidated. Fitness costs associated with escape and magnitude of the epitope-specific T cell response are generally considered to be the key in determining timing of HIV escape...
2018: Frontiers in Immunology
Denise Kühnert, Roger Kouyos, George Shirreff, Jūlija Pečerska, Alexandra U Scherrer, Jürg Böni, Sabine Yerly, Thomas Klimkait, Vincent Aubert, Huldrych F Günthard, Tanja Stadler, Sebastian Bonhoeffer
Drug resistant HIV is a major threat to the long-term efficacy of antiretroviral treatment. Around 10% of ART-naïve patients in Europe are infected with drug-resistant HIV type 1. Hence it is important to understand the dynamics of transmitted drug resistance evolution. Thanks to routinely performed drug resistance tests, HIV sequence data is increasingly available and can be used to reconstruct the phylogenetic relationship among viral lineages. In this study we employ a phylodynamic approach to quantify the fitness costs of major resistance mutations in the Swiss HIV cohort...
February 20, 2018: PLoS Pathogens
Teresa H Evering
PURPOSE OF REVIEW: The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS). RECENT FINDINGS: Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic...
February 19, 2018: Current HIV/AIDS Reports
Richard A Cangelosi, Elissa J Schwartz, David J Wollkind
Analysis of previously published target-cell limited viral dynamic models for pathogens such as HIV, hepatitis, and influenza generally rely on standard techniques from dynamical systems theory or numerical simulation. We use a quasi-steady-state approximation to derive an analytic solution for the model with a non-cytopathic effect, that is, when the death rates of uninfected and infected cells are equal. The analytic solution provides time evolution values of all three compartments of uninfected cells, infected cells, and virus...
2018: Frontiers in Microbiology
Abby May Falla, Sanne Henrietta Ina Hofstraat, Erika Duffell, Susan Josien Maria Hahné, Lara Tavoschi, Irene Karen Veldhuijzen
BACKGROUND: In 2016, the World Health Organisation set a goal to eliminate viral hepatitis by 2030. Robust epidemiological information underpins all efforts to achieve elimination and this systematic review provides estimates of HBsAg and anti-HCV prevalence in the European Union/European Economic Area (EU/EEA) among three at-risk populations: people in prison, men who have sex with men (MSM), and people who inject drugs (PWID). METHODS: Estimates of the prevalence among the three risk groups included in our study were derived from multiple sources...
February 12, 2018: BMC Infectious Diseases
Yue Yang, Xiu-Ping Zhao, Hua-Chun Zou, Min-Jie Chu, Ping Zhong, Xiao-Shan Li, Xiao-Yan Li, Yu-Hui Yu, Ke-Xin Zhu, Yu-Jia Chen, Fei Xia, Bo-Wen Zhu, Luan-Qi Ruan, Yi-Ning Bao, Xun Zhuang
The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic.The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01_AE and CRF07_BC among antiretroviral therapy (ART)-naïve MSM recently infected with HIV-1 in Jiangsu Province.We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015...
February 2018: Medicine (Baltimore)
Umesh Kalathiya, Monikaben Padariya, Maciej Baginski
HIV-1 integrase (IN) is crucial for integration of viral DNA into the host genome and a promising target in development of antiretroviral inhibitors. In this work, six new compounds were designed by linking the structures of two different class of HIV-1 IN inhibitors (active site binders and allosteric IN inhibitors (ALLINIs)). Among newly designed compounds, INRAT10b was found most potent HIV-1 IN inhibitor considering different docking results. To further validate protein-ligand interactions obtained from dockings, molecular dynamics simulations were performed for inhibitor raltegravir and INRAT10b placed either at active site or allosteric site of HIV-1 IN (monomer or dimer)...
February 6, 2018: Biotechnology and Applied Biochemistry
Amy E Baxter, Una O'Doherty, Daniel E Kaufmann
Recent years have seen a substantial increase in the number of tools available to monitor and study HIV reservoirs. Here, we discuss recent technological advances that enable an understanding of reservoir dynamics beyond classical assays to measure the frequency of cells containing provirus able to propagate a spreading infection (replication-competent reservoir). Specifically, we focus on the characterization of cellular reservoirs containing proviruses able to transcribe viral mRNAs (so called transcription-competent) and translate viral proteins (translation-competent)...
February 2, 2018: Retrovirology
Louis R Hollingsworth, Anne M Brown, Richard D Gandour, David R Bevan
Multiple approaches are being utilized to develop therapeutics to treat HIV infection. One approach is designed to inhibit entry of HIV into host cells, with a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have been shown to be effective in inhibiting HIV entry, with a mechanism involving electrostatic interactions with the V3 loop of gp120 being proposed. In this study, we applied computational methods to elucidate molecular interactions between the repeat unit of the precisely alternating polyanion, Poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA) and the V3 loop of gp120 from strains of HIV against which these polyanions were previously tested (IIIb, BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures are available (YU2, 2B4C)...
2018: PloS One
Lalit Deshmukh, Vitali Tugarinov, Daniel H Appella, G Marius Clore
HIV-1 nucleocapsid (NCp7) is a two Cys2HisCys zinc knuckle (N-Zn and C-Zn) protein that plays a key role in viral replication. Here we characterize NCp7 conformational dynamics by NMR relaxation dispersion and chemical exchange saturation transfer measurements. While the N-Zn knuckle is conformationally stable, the C-Zn knuckle interconverts on the millisecond time scale between the major state, in which the zinc is coordinated by three cysteines and a histidine, and two folded minor species (with populations around 1%) in which one of the coordination bonds (Cys413-S---Zn or His421-N2---Zn) is hydrolysed...
January 18, 2018: Angewandte Chemie
Sergio Ita, Alison K Hill, Evan C Lam, Fay J Dufort, Xiao Yang, Ruchi Newman, Sivan Leviyang, Ismael B Fofana, Welkin E Johnson
Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV env gene during early infection (≤ 29 weeks post-infection) in a cohort of four SIVmac251-infected rhesus macaques...
January 17, 2018: Journal of Virology
Ameya R Kirtane, Omar Abouzid, Daniel Minahan, Taylor Bensel, Alison L Hill, Christian Selinger, Anna Bershteyn, Morgan Craig, Shirley S Mo, Hormoz Mazdiyasni, Cody Cleveland, Jaimie Rogner, Young-Ah Lucy Lee, Lucas Booth, Farhad Javid, Sarah J Wu, Tyler Grant, Andrew M Bellinger, Boris Nikolic, Alison Hayward, Lowell Wood, Philip A Eckhoff, Martin A Nowak, Robert Langer, Giovanni Traverso
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases...
January 9, 2018: Nature Communications
Xiao Qian Wang, Sarah Palmer
Antiretroviral therapy effectively suppresses, but does not eradicate HIV-1 infection. Persistent low-level HIV-1 can still be detected in plasma and cellular reservoirs even after years of effective therapy, and cessation of current treatments invariably results in resumption of viral replication. Efforts to eradicate persistent HIV-1 require a comprehensive examination of the quantity and genetic composition of HIV-1 within the plasma and infected cells located in the peripheral blood and tissues throughout the body...
January 9, 2018: Retrovirology
Axel Fun, Thomas Leitner, Linos Vandekerckhove, Martin Däumer, Alexander Thielen, Bernd Buchholz, Andy I M Hoepelman, Elizabeth H Gisolf, Pauline J Schipper, Annemarie M J Wensing, Monique Nijhuis
BACKGROUND: Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance...
January 5, 2018: Retrovirology
Evin Uzun Jacobson, Katherine A Hicks, Emily L Tucker, Paul G Farnham, Stephanie L Sansom
CONTEXT: Human immunodeficiency virus (HIV) incidence and prevalence in the United States are characterized by significant disparities by race/ethnicity. National HIV care goals, such as boosting to 90% the proportion of persons whose HIV is diagnosed and increasing to 80% the proportion of persons living with diagnosed HIV who are virally suppressed, will likely reduce HIV incidence, but their effects on HIV-related disparities are uncertain. OBJECTIVE: We sought to understand by race/ethnicity how current HIV care varies, the level of effort required to achieve national HIV care goals, and the effects of reaching those goals on HIV incidence and disparities...
December 27, 2017: Journal of Public Health Management and Practice: JPHMP
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Isabelle Hardy, Michel Roger
HIV continues to spread among vulnerable heterosexual (HET), Men-having-Sex with Men (MSM) and intravenous drug user (IDU) populations, influenced by a complex array of biological, behavioral and societal factors. Phylogenetics analyses of large sequence datasets from national drug resistance testing programs reveal the evolutionary interrelationships of viral strains implicated in the dynamic spread of HIV in different regional settings. Viral phylogenetics can be combined with demographic and behavioral information to gain insights on epidemiological processes shaping transmission networks at the population-level...
December 28, 2017: Viruses
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