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Serial in vivo passage of HIV-1 infection in Macaca nemestrina.
Agy MB; Schmidt A; Florey M; Kennedy B; Schaffer G; Rodregues H; Katze
January 30, 1997
Int Conf AIDS. 1996 Jul 7-12;11(2):4 (abstract no. We.A.140). Unique

Objective: To examine virological parameters of HIV-1 infection during serial in vivo passage in M. nemestrina. Methods: Twelve pig-tailed macaques were divided into four groups. The pair of macaques in group 1 were inoculated with HIV-1LAI or HIV-1NL4-3. Group 2 contained two macaque pairs each of which received 10 ml of blood from the LAI or NL4-3 animals in group 1. The 4 animals in group 3 received 10 ml of blood from each of the NL4-3 recipients in group 2. The two animals in group 4 were transfused with blood from one of the macaques in group 3. The infections were monitored by virus culture, QC RT PCR, and immunoblots. Several PCR clones spanning the env variable regions 1-5 from each virus-positive macaque were sequenced and examined. Results: Virus was recovered from all but one (93090) of the NL4-3 recipient animals in groups 1-3. No virus was recovered from the group 4 macaques (93112, 93116) nor the LAI transfused animals in group 2 (93094, 93117). No virus was recovered past 10 weeks p.i. All but one macaque in group 4 (93112) had detectable cell-free HIV-1 in the plasma by week 2 or 3 post transfusion. In most cases, plasma virus levels increased over several weeks. All animals in groups 1-3 seroconverted to HIV-1. The sequences obtained from animals late in the passage experiment in group 3 93093 and 93113) did not differ more from the original inoculum virus (HIV-1NL4-3) than those early in the passage experiment 93089) indicating limited genetic drift. Conclusions: HIV-1 infection can be serially passed in M. nemestrina. There was little evidence of genetic adaptation during the 3 serial passages in this experiment; all infections followed similar courses. Each infection began with a burst of replication producing an extracellular plasma viremia followed by seroconversion and disappearance of virus from the peripheral circulation. The ability of M. nemestrina to respond to this initial replication burst and contain the infection suggests that the HIV-1 restriction in these macaques is more a function of the host's response after infection and replication than an actual infection block.

*HIV Infections/PATHOLOGY *HIV-1/PATHOGENICITY *Serial Passage/METHODS *Virus Replication