Host genetic factors that control immune responses to retrovirus infections

Several host genes control retroviral replication and pathogenesis. These include genes that directly affect the replication of retroviruses in target cells and those that control the host immune responses to the viral. antigens. Host genetic factors that affect retroviratal reptication and immune responses to the viratal antigens have been best studied in mouse models of Friend leukemia virus (FV) infection. Several genes Located within the major histocompatibitity comptex (MHC), along with a separate gene not Linked to the MHC, influence the host immune responses to FV antigens. The tatter, the Rfv3, regutates the production of virus-neutratizing antibodies, and thus affects the duration of viremia. T-cell responses to the viral epitopes are controlled by MHC class I and class 11 genotypes, and both CD8(+) and CD4(+) T-cells are required for spontaneous immune resistance to FV infection. When CD4(+) T-helper cells are efficiently primed with a viral epitope, however, CD8(+) T-cells are not required for immune protection against FV infection, white B cells are absolutely required. There are individuals who possess human immunodeficiency virus type I (HIV-1)-reactive IgA antibodies in their mucosal. secretions and show strong T-cell responses to HIV-1 antigens, even though they are negative for HIV-1 genome and HIV-1-reactive serum IgG. These HIV-1-exposed but uninfected individuals rarely possess resistance-associated alleles at known AIDS-restricting loci such as CCR5 Delta 32. Recent genetic analyses have indicated that a Large proportion of such exposed but uninfected individuals may share a common genetic background.(c) 2008 Elsevier Ltd. All rights reserved.