Abstract:
Despite the similarities of SIV-induced AIDS in macaques and HIV-induced AIDS in humans, these two viruses differ in their regulatory genes and in the composition of their envelope genes to a sufficient extent so as to warrant performing vaccine and therapeutic studies with HIV-1 in animals. The expense of maintaining chimpanzees has severely curtailed the use of this species for HIV-1 studies. The PBMC's of pig-tailed macaques have been shown to be unusually susceptible among macaque species to infection in vitro by various strains of HIV-1. Pig-tailed macaques can also be infected in vivo, although all successful infections to date have used large amounts of virus and/or autologously infected macaque PBMC's. The amount of HIV-1 needed to infect pig-tailed macaques is therefore unknown, and is an essential piece of information for the use of this primate model in HIV-1 vaccine and antiviral studies. Accordingly, the titration of a well-characterized stock of HIV-1 (strain III-B, lot 040) has being performed in vivo in these macaques. This lot has previously been titered in chimpanzees in vivo and shown to contain 2.5 x 10(4) animal infectious doses (AID) per ml. Five pairs of pig-tailed macaques have been inoculated intravenously with HIV-1 III-B (lot 040) in doses ranging from 1000 to 0.1 chimpanzee infectious doses (CID). All pigtailed macaques that were inoculated with 1000, 100 or 10 CID seroconverted and virus could be isolated from their PBMC's. The four animals that received 1 and 0.1 CID did not seroconvert, but virus was isolated one time at week 12 from one of the pig-tailed macaques that was inoculated with 1 CID. Although one conclusion from this titration study is that pig-tailed macaques can be infected with 10 CID of HIV-1 III-B, the serological response was not as robust as that of chimpanzees infected with low doses of HIV-1 III-B, or that of macaques infected with low doses of SIV. In addition, the virus load was low (approximately 8 x 10(6) PBMC's were needed to isolate virus), and the frequency of virus isolation was lower than that seen in HIV-1 infected chimpanzees or SIV-infected macaques. Other strains of HIV-1 or serial in vivo passaging of the virus may yield stocks that may be even more infectious.
Keywords: Acquired Immunodeficiency Syndrome/*MICROBIOLOGY Animal Chimpansee troglodytes Comparative Study Human *HIV Seropositivity HIV-1/*PATHOGENICITY Macaca nemestrina Simian Acquired Immunodeficiency Syndrome/MICROBIOLOGY SIV/PATHOGENICITY Virulence ABSTRACT 940730
M9470867
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