Early pathogenesis of SIV genital transmission.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Early pathogenesis of SIV genital transmission.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:31. Unique Identifier : AIDSLINE MED/97927019
Preston A; Aaron Diamond AIDS Research Center, Tuxedo, NY. Fax: (914) 351-2015.

Abstract: The rhesus (Rh) macaque genital transmission model uses simian immunodeficiency virus (SIV) to address early steps of pathogenesis, vaccine protection and co-factors of transmission. Dual tropic SIVmac, readily crosses the intact epithelium of the penile urethra, vagina or rectum. Dual tropic simian-human immunodeficiency virus (SHIV) 89.6 and T cell tropic SHIV33, but not macrophage tropic SHIV162 infect via the vagina. ln all cases, the mucosa was a strong barrier to infection. Cell-associated SIV was not infectious in the vaginal model. The course to disease was relatively rapid compared to human (hu), with disease in 3 to 6 months in rapid progressors (RP), 6 months to 3 years in progressors and over 3 years in a small minority. RP were characterized by high virus load and low antibody at 60 to 90 days post-infection. Vaginal cellular and humoral immune responses were induced and implants containing the female sex hormone, progesterone, enhanced transmission compared to the normal follicular phase. Early events, including entry, have been characterized. Infected dendritic cells (DC) were identified in vivo during the first week of infection and DCs plus resting T cells support in vitro replication of SIVmac. Rh and hu CCR5 were co-receptors for divergent SIVs, SIVmac, SIVsm and SIV chimpanzee cpz). DNA sequencing of rh, sooty mangabey and cpz CCR5 showed close homology to hu CCR5. All SIVs tested used all CCR5s but not CxCR4. However they were dual tropic, apparently using an unknown T cell co-receptor. The macaque genital transmission model remains a good means of exploration of pathogenesis and immunity to SIV.

Keywords: *Genitalia/IMMUNOLOGY *SIV/PHYSIOLOGY
971130
M97B1199

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