Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome.

ABSTRACT: The diversity of HIV-1 and human genetics complicates our ability to determine the impact of treatment during primary HIV-1 infection on disease outcome. Here, we show, in a small group infected with virtually identical HIV-1 strains and treated during primary HIV-1 infection, that patients expressing protective human leucocyte antigen alleles had lower viral loads following treatment discontinuation. These data suggest that genetic factors play an important role in the outcome of HIV-1 infection despite early therapy.

SUBMITTER: Streeck H

PROVIDER: S-EPMC3082841 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome.

Streeck Hendrik H Jessen Heiko H Kuecherer Claudia C Li Bin B Jessen Arne B AB Dupke Stephan S Baumgarten Axel A Stahmer Ingrid I van Lunzen Jan J Altfeld Marcus M Walker Bruce D BD Allen Todd M TM

AIDS (London, England) 20090101 2

The diversity of HIV-1 and human genetics complicates our ability to determine the impact of treatment during primary HIV-1 infection on disease outcome. Here, we show, in a small group infected with virtually identical HIV-1 strains and treated during primary HIV-1 infection, that patients expressing protective human leucocyte antigen alleles had lower viral loads following treatment discontinuation. These data suggest that genetic factors play an important role in the outcome of HIV-1 infectio ...[more]

PMID: 19098497

Similar Datasets

Functional relevance of nonsynonymous mutations in the HIV-1 tat gene within an epidemiologically-linked transmission cohort.

Project description:Here we investigated the nature and functional consequences of mutations in the HIV-1 tat gene within an epidemiologically-linked AIDS transmission cohort consisting of a non-progressing donor (A) and two normal progressing recipients (B and C). Multiple nonsynonymous mutations in the tat first exon were observed across time in all individuals. Some mutations demonstrated striking host specificity despite the cohort being infected with a common virus. Phylogenetic segregation of the tat clones at the time of progression to AIDS was also observed especially in recipient C. Tat clones supporting high levels of transactivation were present at all time points in all individuals, although a number of clones defective for transactivation were observed for recipient C in later time points. Here we show that the tat quasispecies in a linked transmission cohort diversify and evolve independently between hosts following transmission. It supports the belief that quasispecies variation in HIV-1 is a mechanism for selection towards defining a fitter gene variant that is capable of resisting the human immune system.

| S-EPMC2174444 | biostudies-literature

Host factors that influence mother-to-child transmission of HIV-1: genetics, coinfections, behavior and nutrition.

Project description:Mother-to-child transmission (MTCT) is the most important mode of HIV-1 acquisition among infants and children and it can occur in utero, intrapartum and postnatally through breastfeeding. Great progress has been made in preventing MTCT through use of antiretroviral regimens during gestation, labor/delivery and breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain incompletely understood. This review focuses on select host factors affecting MTCT, in particular genetic factors, coexisting infections, behavioral factors and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1 viral load, an important determinant of MTCT, through use of antiretroviral agents, complementary focus on overall maternal health is often neglected. By addressing coinfections in mothers and infants, improving the mother's nutritional status and modifying risky behaviors and practices, not only is maternal and child health improved, but a direct benefit in reducing MTCT can be derived. The study of genetic variations in susceptibility to HIV-1 infection is rapidly evolving, and the future is likely to bring revolutionary changes in HIV-1 prevention by enhancing natural resistance to infection and by individually tailoring pharmacologic regimens.

| S-EPMC5769959 | biostudies-other

Three-dimensional imaging of HIV-1 virological synapses reveals membrane architectures involved in virus transmission.

Project description:HIV transmission efficiency is greatly increased when viruses are transmitted at virological synapses formed between infected and uninfected cells. We have previously shown that virological synapses formed between HIV-pulsed mature dendritic cells (DCs) and uninfected T cells contain interdigitated membrane surfaces, with T cell filopodia extending toward virions sequestered deep inside invaginations formed on the DC membrane. To explore membrane structural changes relevant to HIV transmission across other types of intercellular conjugates, we used a combination of light and focused ion beam scanning electron microscopy (FIB-SEM) to determine the three-dimensional (3D) architectures of contact regions between HIV-1-infected CD4(+) T cells and either uninfected human CD4(+) T cells or human fetal astrocytes. We present evidence that in each case, membrane extensions that originate from the uninfected cells, either as membrane sheets or filopodial bridges, are present and may be involved in HIV transmission from infected to uninfected cells. We show that individual virions are distributed along the length of astrocyte filopodia, suggesting that virus transfer to the astrocytes is mediated, at least in part, by processes originating from the astrocyte itself. Mechanisms that selectively disrupt the polarization and formation of such membrane extensions could thus represent a possible target for reducing viral spread.Our findings lead to new insights into unique aspects of HIV transmission in the brain and at T cell-T cell synapses, which are thought to be a predominant mode of rapid HIV transmission early in the infection process.

| S-EPMC4178837 | biostudies-other

Host genetics and HIV-1: the final phase?

Project description:This is a crucial transition time for human genetics in general, and for HIV host genetics in particular. After years of equivocal results from candidate gene analyses, several genome-wide association studies have been published that looked at plasma viral load or disease progression. Results from other studies that used various large-scale approaches (siRNA screens, transcriptome or proteome analysis, comparative genomics) have also shed new light on retroviral pathogenesis. However, most of the inter-individual variability in response to HIV-1 infection remains to be explained: genome resequencing and systems biology approaches are now required to progress toward a better understanding of the complex interactions between HIV-1 and its human host.

| S-EPMC2954832 | biostudies-literature

Virological Outcome Measures During Analytical Treatment Interruptions in Chronic HIV-1-Infected Patients.

Project description:Background:Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies. Methods:We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated. Results:The set point was lower than baseline VL (median delta set point, -0.26; P < .001). This difference was >1 log10 copies/mL in 13.9% of the cases. The median TtR was 2 weeks; no patients had an undetectable VL at week 12. The median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions. Conclusions:TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

| S-EPMC7047957 | biostudies-literature

CIDR-NIDA Study of HIV Host Genetics

Project description:CIDR-NIDA Study of HIV Host Genetics

| PRJNA83629 | ENA

Host genetics determine susceptibility to avian influenza infection and transmission dynamics.

Project description:Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra-nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFN? secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds.

| S-EPMC4899695 | biostudies-literature

Impact of pre-adapted HIV transmission.

Project description:Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.

| S-EPMC4899163 | biostudies-literature

Favipiravir and Ribavirin Treatment of Epidemiologically Linked Cases of Lassa Fever.

Project description:Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.

| S-EPMC5682919 | biostudies-literature

A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits.

Project description:Diseases often cooccur in individuals more often than expected by chance, and may be explained by shared underlying genetic etiology. A common approach to genetic overlap analyses is to use summary genome-wide association study data to identify single-nucleotide polymorphisms (SNPs) that are associated with multiple traits at a selected P-value threshold. However, P-values do not account for differences in power, whereas Bayes' factors (BFs) do, and may be approximated using summary statistics. We use simulation studies to compare the power of frequentist and Bayesian approaches with overlap analyses, and to decide on appropriate thresholds for comparison between the two methods. It is empirically illustrated that BFs have the advantage over P-values of a decreasing type I error rate as study size increases for single-disease associations. Consequently, the overlap analysis of traits from different-sized studies encounters issues in fair P-value threshold selection, whereas BFs are adjusted automatically. Extensive simulations show that Bayesian overlap analyses tend to have higher power than those that assess association strength with P-values, particularly in low-power scenarios. Calibration tables between BFs and P-values are provided for a range of sample sizes, as well as an approximation approach for sample sizes that are not in the calibration table. Although P-values are sometimes thought more intuitive, these tables assist in removing the opaqueness of Bayesian thresholds and may also be used in the selection of a BF threshold to meet a certain type I error rate. An application of our methods is used to identify variants associated with both obesity and osteoarthritis.

| S-EPMC4832282 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data