AEGiS-15IAC: Early virological events in various tissues of adult and newborn macaques after intrarectal infection with pathogenic SHIV.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Early virological events in various tissues of adult and newborn macaques after intrarectal infection with pathogenic SHIV.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1440)

Miyake A, Ibuki K, Enose Y, Suzuki H, Horiuchi R, Saito N, Nakasone T, Honda M, Miura T, Hayami M
Institute for Virus Research, Kyoto University, Kyoto, Japan

BACKGROUND: Information on virological events soon after HIV infection is important for vaccine study but limited. In this study, we examined the virus distribution and replication in various tissues within one month after mucosal infection using SHIV-macaque model.

METHODS: Adult and newborn rhesus macaques were inoculated intrarectally with a pathogenic SHIV-C2/1KS661c. In various tissues of adults at 3, 6, 13 and 27 days post inoculation (dpi) and those of newborns at 14 and 26 dpi, proviral DNA and infectious virus were quantified and proportion of CD4+ T cells was calculated.

RESULTS: In adults, proviral DNA was detected at 3 dpi in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious viruses were first detected at 6 dpi and a high level of proviral DNA and infectious viruses were detected at 13 dpi. By 27 dpi, infectious viruses decreased profoundly although proviral DNA load remained unaltered. In intestinal tracts, infectious viruses were almost not detected throughout the infection although proviral DNA was detected at the same level as in lymphoid tissues. In newborns, infectious viruses were detected in the thymus more conspicuously than in adults between 14 and 26 dpi. However, CD4+ T cells in the thymus declined after 14 dpi and most of CD4+ cells at 26 dpi were immature (CD3-) T cells.

CONCLUSIONS: These results showed that the virus quickly spread to systemic tissues after the mucosal transmission. In adults, infectious viruses were actively produced in the lymphoid tissues but later they became latent. In contrast, in intestinal tracts, they remained latent throughout the infection. In newborns, the thymus was a main site of virus replication and the virus was suggested to be produced from not only mature but also immature CD4+ T cells.

Keywords: AEGIS, Macaca, Communicable Diseases, Macaca mulatta, CD4-Positive T-Lymphocytes, HIV Infections, Virus Replication, Lymphoid Tissue, Adult, Infant, Newborn, Animal, Humans, virology

040711
ThOrA1440