Muenk C, Kootstra NA, Lucero G, Brandt SM, Verma IM, Landau NR; Conference on Retroviruses and Opportunistic Infections.
Abstr 10th Conf Retrovir Oppor Infect Feb 10 14 2003 Hynes Conv Cent Boston Mass USA Conf Retrovir Oppor Infect 10th 2003 Boston Mass. 2003 Feb 10-14; 10: abstract no. 201.
Salk Inst for Biological Studies, La Jolla, CA
BACKGROUND: HIV-1 does not infect nonhuman primates and replicates poorly or not all on activated nonhuman primate lymphocytes in vitro. We analyzed the basis of the block to HIV-1 replication in nonhuman primate cells. A cellular protein, APOBEC3G/CEM15 interferes with HIV replication in viruses that lack a functional VIF gene. Depending on the specificity of the primate homologue of APOBEC3G, it is possible that this protein is one of the elements that blocks HIV replication in primate cells.METHODS: Human and simian cells were infected with HIV, SIV, and lentiviral reporter viruses. Infection was monitored by real-time PCR. Mutations in the capsid gene were used to map the viral determinants involved into the restriction.RESULTS: HIV-1 reverse transcription did not initiate efficiently in the primate cells. The block was overridden at MOI >1 or by pre-incubation of the nonhuman primate cells with virus. Heterokaryon analysis suggested that the primate cells contain a dominant inhibitor of HIV-1 reverse transcription. Lentiviral vectors containing point mutations in the capsid more efficiently infected the primate cells. Dual infection experiments suggested that the inhibitor interacts with the capsid protein. The mutation that relieved the post-entry restriction in primate cells was located near the cyclophilin A binding region. CV-1 African Green monkey cells were found to express abundance quantities of APOBEC3G. The effects of this protein on HIV-1 and SIV replication will be reported.CONCLUSIONS: HIV-1 replication in monkeys is restricted by a cellular inhibitor that acts at reverse transcription, most likely by targeting the capsid of the virus. VIF may also play a role in determining the host range of HIV-1.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Capsid
- Genes, gag
- Genes, vif
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- In Vitro
- Primates
- Reverse Transcription
- Simian immunodeficiency virus
- genetics
Other ID:
UI: 102260242
From Meeting Abstracts