title: Does AID aid AIDS?
abstract: During AIDS, the acquisition of mutations in the HIV-1 gp120 envelope glycoprotein leads to the switch from primary R5 (CCR5-using) to highly cytopathic X4 (CXCR4-using) HIV-1 variants. Based on the already known sequence homology between IgV genes and the gp120-coding region of the env gene, as well as on somatic hypermutation of multiple proto-oncogenes, the somatic hypermutation hypothesis for the mechanism of R5-X4 HIV-1 switching is proposed as follows. This switch takes place in the germinal center (GC) B cells due to the aberrant somatic hypermutation of the gp120-coding part of the HIV-1 env gene. Activation-induced cytidine deaminase (AID) is required for this process. Activation through IL4R and CD40 is required both for infection of GC B cells with HIV-1 and for induction of AID expression in the same cells. B cell infection with R5 HIV-1 variants is the limiting stage in the process of the viral phenotypic switch during the asymptomatic period of AIDS. Overall up-regulation of CXCR4 coreceptor on the GC B cells and the CD4(+) T cells surrounding the GC provides the predominant replication and acquisition of the newly formed X4 HIV-1 variants.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Suslov
mesh_terms: D003564:Cytidine Deaminase / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase