Mutational Evidence for an Internal Fusion Peptide in Flavivirus Envelope Protein E

Abstract

Most human immunodeficiency virus (HIV) type 1 infections occur by the mucosal route. Thus, it is important to assess the immune responses to HIV in the vaginal, cervical, and rectal compartments. Here we quantitated the virus-specific CD8⁺ T-cell response and characterized the phenotype of lymphocytes in the genital tracts of naive macaques, macaques acutely or chronically infected with simian immunodeficiency virus SIV_mac251, and macaques chronically infected with chimeric simian/human immunodeficiency virus SHIV_KU2. Vaginal biopsy samples or samples obtained at the time of euthanasia were used in this analysis. The percentage of Gag-specific, tetramer-positive T cells was as high as 13 to 14% of the CD3⁺ CD8⁺ T-cell population in the vaginal and cervical laminae propriae of both SIV_mac251 and SHIV_KU2 chronically infected macaques. In most cases, the frequency of this response in the cervicovaginal compartment far exceeded the frequency in the blood or the draining iliac lymph node. Vaginal laminae propriae of naive macaques contained 55 to 65% CD3⁺ CD8⁺ cells and 28 to 34% CD3⁺ CD4⁺ cells, while the majority of intraepithelial cells were CD8⁺ T cells (75 to 85%). For the same cells, the surface expression of CD62L was low whereas that of αEβ7 was high. No difference in the expression of CD45RA on CD8⁺ T cells was observed in the chronic stage of SIV_mac251 infection. Although no decrease in the percentage of CD4⁺ cells in the genital tract was observed within the first 12 days of infection, by 6 weeks from SIV_mac251 infection and thereafter the percentage of CD4⁺ T cells was decreased in the laminae propriae of the vagina and cervix. Expression of CD45RA did not differ in naive and acutely SIV_mac251 infected macaques. Information on the quality and quantity of local immune responses may help in the design of vaccine strategies aimed at containing viral replication at the site of viral encounter.