Abstract:
We investigated molecular variations of HIV-2 env gene in experimentally infected rhesus macaques involved in a vaccinal trial. Fourteen rhesus macaques were treated as follows: 5 monkeys were vaccinated with recombinant vaccinia viruses expressing gag, pol, nef and vif, genes of HIV-2Rod, 5 monkeys received the same mixture plus a recombinant virus expressing env gene. One monkey only received the wild vaccinia virus. The challenge was performed with an heterologous viral strain HIV-2Sb16669/H5; 3 naives monkeys were used as challenge control. Serological follow-up, PBMC cocultures, PCR on PBMCs clearly demonstrated that all the monkeys were persistently infected over a period of 521 days after challenge. None of the vaccinal mixtures protected the animals from infection. Moreover, RT-PCR on sera evidenced that an active viral replication continuously occurred in most of the animals. Two monkeys developed clinical symptoms which might be related to their viral infection: 1 had neurological symptoms, and was sacrificed 136 days after the challenge; an other one presented a wasting syndrome since the 16th month. A region of HIV-2 gp105 gene encompassing the V3 and V4 hypervariable domains was directly sequenced by Sanger's method on purified PCR products. Low variations were observed in viral sequences in PBMCs and sera from all the animals and in viral isolates from monkey cell cultures, during the 17 months following the challenge. No vaccination specific mutation was detected. As observed in HIV-1 infected humans, variation of the hypervariable V3 and V4 domains appears to be low in peripheral blood during the first 520 days of the macaque rhesus infection. Our results reemphasized the usefullness of the HIV-2 infected macaques as an animal model of HIV infection.
Keywords: Acquired Immunodeficiency Syndrome/IMMUNOLOGY/MICROBIOLOGY Animal *Genes, env Genes, gag Genes, nef Genes, pol Genes, vif Human HIV-1 HIV-2/*GENETICS/IMMUNOLOGY/*ISOLATION & PURIF Macaca mulatta Polymerase Chain Reaction Simian Acquired Immunodeficiency Syndrome/*GENETICS/IMMUNOLOGY/ PREVENTION & CONTROL *Vaccines, Synthetic Variation (Genetics) *Viral Vaccines Virus Replication ABSTRACT 940730
M9470868
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