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 retroviral replication and immune responses to the viral antigens have been best studied in mouse models of Friend leukemia virus (FV) infection. Several genes located within the major histocompatibility complex (MHC), along with a separate gene not linked to the MHC, influence the host immune responses to FV antigens. The latter, the Rfv3, regulates the production of virus-neutralizing antibodies, and thus affects the duration of viremia. T-cell responses to the viral epitopes are controlled by MHC class I and class II 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, while B cells are absolutely required. There are individuals who possess human immunodeficiency virus type 1 (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 CCR5Delta32. Recent genetic analyses have indicated that a large proportion of such exposed but uninfected individuals may share a common genetic background.
Miyazawa
Masaaki
M
Department of Immunology, Kinki University School of Medicine, Osaka 589-0023, Japan. masaaki@med.kindai.ac.jp
Tsuji-Kawahara
Sachiyo
S
Kanari
Yasuyoshi
Y
D000818:Animals; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology*; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D018023:HIV Seronegativity; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology* / Q000821:virology; D051379:Mice; D010641:Phenotype; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D015483:HIV Antibodies