Influence of Host Genetic Variation on Susceptibility to HIV Type 1 Infection

Abstract

For this review of genetic susceptibility to human immunodeficiency virus type 1 infection, far more information was available on factors involved in acquisition of the virus by an uninfected "recipient" than on propagation by the infected "donor." Genetic variation presumably alters transmission from an infected host primarily by regulating the replication of virus and the concentration of particles circulating in blood and mucosal secretions of the potential donor. Thus, the effects of host genetic variation on transmission are inextricably bound to the well-established and powerful effects on virus load at different stages of infection. Teasing apart the effects in both donors and recipients has been and will continue to be quite difficult.

Suppressed cellular alloimmune responses in HIV-exposed seronegative female sex workers

“…In addition to the induction of alloimmune responses, differential HLA-restricted epitope recognition by HIV-specific CTL in recipient and donor, and HLA-KIR interactions that regulate NK cell activity have been proposed [36,37]. The present data could at least suggest that the putative anti-HIV activity of HLA does not depend on activated alloimmune responses.…”

“…Flow cytometry detection of CD69 in one way MLRs is a well-established alternative for 3 H-thymidine incorporation [36]. As an alternative for irradiation, we have shown the superiority of PFA over MMC and AMD for the inactivation of stimulator cells.…”

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

“…1,2 Major histocompatibility complex (MHC) class I antigens that present foreign peptides can activate cytotoxic T lymphocytes (CTL), which are crucial for containing viral replication. Several studies have shown (1) a temporal relationship between the decline of viral load and the emergence of CTL responses in both infected humans and infected monkeys, [3][4][5][6] (2) an increase of viral load after the appearance of CTL-escape HIV/SIV mutants during chronic and acute infection [7][8][9][10][11][12][13] and (3) a dramatic rise of viral load after CD8 þ T-cell depletion. [14][15][16] Additional indirect evidence for a CTL effect upon viral replication came from genetic association studies showing that Mhc class I alleles are strongly associated with survival time in HIV-infected humans [17][18][19][20] .…”

Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity

“…[18][19][20][21] Subtype differences may also impact responses to antiretroviral therapies, 5,22 and host genetic determinants of susceptibility and progression to AIDS may vary according to infecting HIV-1 subtype. 6,23 The limited number of virus isolates currently available for assay development, pharmaceutical design, and the evaluation of intervention strategies constrains the ability to correctly target viral infections in different geographic regions and to control the spread of HIV. Virus panels that are currently available for assay development and evaluations were isolated more than a decade ago 24,25 and are no longer fully representative of viruses currently in circulation.…”