Kunstman K, Wolinsky S, Agy M, Shibata R, Yoder A, Jones M, Marx P, Chen Z; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 5th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 5th 1998 Chic Ill. 1998 Feb 1-5; 5th: 87 (abstract no. 48).
Northwestern University, Chicago, IL.
Divergent SIV strains use the CCR5 co-receptor together with CD4 for entry into target cells. CCR5 usage by divergent strains of SIV has not been established, however, as co-receptors and replication-competent primary viruses derived from the particular simian and prosimian hosts have not been tested. Primary SIV strains (SlVsmSL92b and SlVsmFNJ) were isolated from cells obtained from two sooty mangabeys by co-cultivation with uninfected cells from the native host. CCR5 was amplified from DNA from blood cells obtained from several species of Prosimians (lemur, bushbaby, loris and tarsier), New World Monkeys (tamarin, marmoset, black howler and owl monkey), Old World Monkeys (diana monkey, M. facicularis, M. fuscata, M. mulatta, M. tonkeana, M. nemestrina and baboon) and apes (gorilla, chimpanzee and orangutan) using primers flanking the exon, cloned and sequenced (both alleles, 97% C.I.). Expression of the CCR5 protein was assessed by a transient transfection assay. Deduced amino acid sequence alignment of the product DNAs showed conserved amino acid changes relative to human CCR5 that accumulated in relationship to the primates position on the evolutionary tree. Phylogenetic reconstructions of the CCR5 proteins recapitulated the evolutionary tree. Co-receptor usage was determined by co-culturing primary HIV-1, HIV-2 and SlVsm strains with established U87MG.CD4 and HOS.CD4 cells constitutively expressing the CCR5 protein derived from each of these primates. While these data show that CCR5 from nonhuman primates may support HIV-1 entry, altered CCR5 expression, blocks to post-entry events and alternative co-receptor usage are likely to play an additional role in viral pathogenesis.
Publication Types:
Keywords:
- Animals
- Antigens, CD4
- CD4-Positive T-Lymphocytes
- Cercocebus atys
- HIV-1
- HIV-2
- Haplorhini
- Humans
- Leontopithecus
- Platyrrhini
- Receptors, CCR5
- Simian immunodeficiency virus
- Strepsirhini
- immunology
Other ID:
UI: 102235629
From Meeting Abstracts