HIV-1 host interactions: integration of large-scale datasets

HIV-1 replication and viral pathogenesis are dependent on numerous host factors. A series of recent papers apply genome-wide and large-scale approaches to map host-virus interactions and to identify host proteins capable of restricting (that is, controlling) the virus. Strategies include genome-wide association studies, small interfering RNA screens, genome-wide transcriptome profiling, proteome studies, and the assessment of the role of host-encoded microRNAs in infection. The various layers of large-scale data are brought together through meta-analytical procedures

Host genome influences on susceptibility to HIV-1

In vitro and in vivo analyses identified a significant component of heritability in cellular or host susceptibility to HIV-1. The bases for susceptibility can be traced to genetic differences (inter-species) resulting from evolutionary adaptation to exogenous (and endogenous) retroviral infections, and to intra-species and inter-individual (human) differences associated with genetic variation. We have completed large scale evolutionary analysis of genes involved in HIV life cycle and pathogenesis, as well as participating and conducting genome-wide association studies, linkage analysis, and transcriptome analysis. These studies allowed a better understanding of the influence of common human variants in HIV-1 susceptibility and define a number of experimental challenges in the filed: understanding of the role of rare and private mutations in susceptibility, and the development of better tools for the integration of data from large-scale studies

Genomic Approaches to the Study of HIV-1 Acquisition

Host genome studies are increasingly available for the study of infectious disease susceptibility. Current technologies include large-scale genotyping, genome-wide screens such as transcriptome and silencing (silencing RNA) studies, and increasingly, the possibility to sequence complete genomes. These approaches are of interest for the study of individuals who remain uninfected despite documented exposure to human immunodeficiency virus type 1. The main limitation remains the ascertainment of exposure and establishing large cohorts of informative individuals. The pattern of enrichment for CCR5 Δ32 homozygosis should serve as the standard for assessing the extent to which a given cohort (of white subjects) includes a large proportion of exposed uninfected individual

Genetic screening for metabolic and age-related complications in HIV-infected persons

Genetic screening for HIV-related complications is emerging as a clinically relevant prediction tool. A number of single nucleotide polymorphisms associated with conditions such as dyslipidemia and type 2 diabetes have been identified in both the general population and in HIV-infected individuals. Additionally, genome-wide association studies have looked at hepatitis C susceptibility in HIV-infected people, and genetic studies are ongoing for coronary artery disease, osteoporosis, and neurocognitive dysfunction. To date, understanding the contribution of genetic variation to the pathogenesis of lipoatrophy and kidney disease in HIV-infection is limited

Genetic, ethnic, and gender differences in the pharmacokinetics of antiretroviral agents

Variable antiretroviral therapy (ART) drug response likely reflects the combined influence of environment, underlying disease, concurrent drugs, and genetics. Gender exerts modest or negligible effects on ART disposition, and it is expected to have limited clinical implication, although it should be accounted for in large population studies. Ethnic denominations have, with the notable exception of efavirenz, no clear influence on ART disposition. Exploration of genetic factors might offer a better comprehension to the largely unpredictable and unresolved variability in ART concentrations and related toxicity or treatment outcome. Despite the negative perception of genetic research among the general public, this type of investigation is now widely accepted by concerned parties: patients, relatives, and study volunteer