scholarly journals The impact of host genetic variation on infection with HIV-1

2015 ◽  
Vol 16 (6) ◽  
pp. 577-583 ◽  
Author(s):  
Paul J McLaren ◽  
Mary Carrington
Keyword(s):  
Genetic Variation ◽  
Host Genetic ◽  
The Impact ◽  
Hiv 1

scholarly journals Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study

2018 ◽  
Author(s):  
Yolanda Guillén ◽  
Marc Noguera-Julian ◽  
Javier Rivera ◽  
Maria Casadellà ◽  
Muntsa Rocafort ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Methanogenic Archaea ◽  
Genetic Associations ◽  
Host Genetics ◽  
Genetic Landscape ◽  
Host Genetic ◽  
Gene Richness ◽  
The Impact ◽  
Hiv 1

AbstractThe impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the host’s genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.

scholarly journals Feedback Between Coevolution and Epidemiology Can Help or Hinder the Maintenance of Genetic Variation in Host-Parasite Models

2020 ◽  
Author(s):  
Ailene MacPherson ◽  
Matthew J. Keeling ◽  
Sarah P. Otto
Keyword(s):  
Genetic Variation ◽  
Population Fluctuations ◽  
Red Queen ◽  
Neutral Drift ◽  
Disease Epidemiology ◽  
Two Factors ◽  
Population Sizes ◽  
Host Genetic ◽  
Host Parasite ◽  
The Impact

AbstractUnderstanding if and when coevolution helps maintains genetic variation in hosts of a directly-transmissible pathogen is fundamental to quantifying the prevalence and impact of coevolution on disease epidemiology. Here, we extend our previous work on the maintenance of genetic variation in a classic matching-alleles coevolutionary model by exploring the effects of ecological and epidemiological feedbacks, where both allele frequencies and population sizes are allowed to vary over time. In general, we find that coevolution rarely maintains more host genetic variation than expected under neutral genetic drift alone. When and if coevolution maintains or depletes genetic variation relative to neutral drift is determined, predominantly, by two factors: the deterministic stability of the Red Queen allele frequency cycles and the frequency at which pathogen fixation occurs, as this results in directional selection and the depletion of genetic variation in the host. Compared to purely coevolutionary models with constant host and pathogen population sizes, ecological and epidemiological feedbacks stabilize Red Queen cycles deterministically, but population fluctuations in the pathogen increase the rate of pathogen fixation, especially in epidemiological models. Taken together our results illustrate the importance of considering the ecological and epidemiological context in which coevolution occurs when examining the impact of Red Queen cycles on genetic variation.

scholarly journals FcγR Genetic Variation and HIV-1 Vaccine Efficacy: Context And Considerations

2021 ◽  
Vol 12 ◽  
Author(s):  
Ria Lassaunière ◽  
Caroline T. Tiemessen
Keyword(s):  
Genetic Variation ◽  
Vaccine Efficacy ◽  
Potential Contribution ◽  
Efficacy Trials ◽  
Receptor Locus ◽  
Host Genetic ◽  
Mother To Child ◽  
Ig G ◽  
Hiv 1

Receptors for the crystallisable fragment (Fc) of immunoglobulin (Ig) G, Fcγ receptors (FcγRs), link the humoral and cellular arms of the immune response, providing a diverse armamentarium of antimicrobial effector functions. Findings from HIV-1 vaccine efficacy trials highlight the need for further study of Fc-FcR interactions in understanding what may constitute vaccine-induced protective immunity. These include host genetic correlates identified within the low affinity Fcγ-receptor locus in three HIV-1 efficacy trials – VAX004, RV144, and HVTN 505. This perspective summarizes our present knowledge of FcγR genetics in the context of findings from HIV-1 efficacy trials, and draws on genetic variation described in other contexts, such as mother-to-child HIV-1 transmission and HIV-1 disease progression, to explore the potential contribution of FcγR variability in modulating different HIV-1 vaccine efficacy outcomes. Appreciating the complexity and the importance of the collective contribution of variation within the FCGR gene locus is important for understanding the role of FcγRs in protection against HIV-1 acquisition.

scholarly journals Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response

2012 ◽  
Vol 2012 ◽  
pp. 1-16
Author(s):  
Raghavan Sampathkumar ◽  
Elnaz Shadabi ◽  
Ma Luo
Keyword(s):  
Genetic Variation ◽  
Vaccine Development ◽  
Therapy Response ◽  
Divergent Evolution ◽  
Sequence Database ◽  
Host Genetic ◽  
Per Se ◽  
Tremendous Challenge ◽  
Hiv 1 ◽  
Hiv Aids

As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomenaper seposes tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response.

scholarly journals Evaluating the Impact of Functional Genetic Variation on HIV-1 Control

2017 ◽  
Vol 216 (9) ◽  
pp. 1063-1069 ◽  
Author(s):  
Paul J McLaren ◽  
Sara L Pulit ◽  
Deepti Gurdasani ◽  
Istvan Bartha ◽  
Patrick R Shea ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Functional Genetic Variation ◽  
The Impact ◽  
Hiv 1

scholarly journals STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lorena Leticia Peixoto de Lima ◽  
Allysson Quintino Tenório de Oliveira ◽  
Tuane Carolina Ferreira Moura ◽  
Ednelza da Silva Graça Amoras ◽  
Sandra Souza Lima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Α Level ◽  
The Impact ◽  
Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

The impact of founder events and introductions on genetic variation in the muskox Ovibos moschatus in Sweden

2011 ◽  
Vol 56 (4) ◽  
pp. 305-314 ◽  
Author(s):  
Carl-Gustaf Thulin ◽  
Linda Englund ◽  
Göran Ericsson ◽  
Göran Spong
Keyword(s):  
Genetic Variation ◽  
Ovibos Moschatus ◽  
Founder Events ◽  
The Impact

scholarly journals The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T cells

2009 ◽  
Vol 207 (1) ◽  
pp. 39-49 ◽  
Author(s):  
Nicoletta Casartelli ◽  
Florence Guivel-Benhassine ◽  
Romain Bouziat ◽  
Samantha Brandler ◽  
Olivier Schwartz ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Adaptive Immune System ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Hiv Replication ◽  
Viral Infectivity Factor ◽  
Cellular Immune ◽  
Vif Protein ◽  
The Impact ◽  
Hiv 1

The cytidine deaminase APOBEC3G (A3G) enzyme exerts an intrinsic anti–human immunodeficiency virus (HIV) defense by introducing lethal G-to-A hypermutations in the viral genome. The HIV-1 viral infectivity factor (Vif) protein triggers degradation of A3G and counteracts this antiviral effect. The impact of A3G on the adaptive cellular immune response has not been characterized. We examined whether A3G-edited defective viruses, which are known to express truncated or misfolded viral proteins, activate HIV-1–specific (HS) CD8+ cytotoxic T lymphocytes (CTLs). To this end, we compared the immunogenicity of cells infected with wild-type or Vif-deleted viruses in the presence or absence of the cytidine deaminase. The inhibitory effect of A3G on HIV replication was associated with a strong activation of cocultivated HS-CTLs. CTL activation was particularly marked with Vif-deleted HIV and with viruses harboring A3G. Enzymatically inactive A3G mutants failed to enhance CTL activation. We also engineered proviruses bearing premature stop codons in their genome as scars of A3G editing. These viruses were not infectious but potently activated HS-CTLs. Therefore, the pool of defective viruses generated by A3G represents an underestimated source of viral antigens. Our results reveal a novel function for A3G, acting not only as an intrinsic antiviral factor but also as an inducer of the adaptive immune system.

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

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