Primary simian immunodeficiency virus (SIV) isolated from sooty mangabey (SIVsm [=

Primary simian immunodeficiency virus (SIV) isolated from sooty mangabey (SIVsm [= 6]) stumptail (SIVstm [= 1]) mandrill (SIVmnd [= 1]) and African green (SIVagm [= 1]) primates were examined for their ability to infect human cells and for their coreceptor requirements. for viral entry similar to what has been described for human immunodeficiency viruses. Chemokine receptors (primarily CCR5 and CXCR4) are the major coreceptors used by human immunodeficiency virus type 1 (HIV-1) for viral entry. In general macrophage-tropic non-syncytium-inducing HIV-1 isolates use CCR5 for entry while T-cell-tropic syncytium-inducing viruses use CXCR4 or multiple coreceptors including CCR1 to CCR5 CXCR4 and GPR15 (also called BOB) (2 3 4 11 14 20 45 47 Recent studies have also suggested that a switch in coreceptor use from CCR5 to CXCR4 or to multiple coreceptors correlates with disease progression (10 46 HIV-2 strains have similar tropism in which the predominant coreceptor used is CCR5. However other coreceptors including CCR1 to CCR5 CXCR4 STRL33 (also called Bonzo) and GPR15 can also be used by some HIV-2 strains (6 23 32 37 43 A. Heredia A. Vallejo V. Soriano J. S. Epstein and I. K. Hewlett Letter AIDS 11:1198-1199 1997 Likewise while CCR5 is known to be a coreceptor for simian immunodeficiency viruses (SIVs) until recently CXCR4 was thought not to function as a coreceptor for SIV even by laboratory-adapted strains (7 15 24 26 29 30 42 The inability of Rabbit polyclonal to ZGPAT. SIV isolates to use CXCR4 but to grow in CD4+ CCR5? human cells led to the discovery of two orphan receptors STRL33 (17 19 G. Alkhatib F. Liao E. A. Berger J. M. Farber and K. W. Peden Letter Nature 388:238 1997 and GPR15 (12 17 19 which have been shown to be used by many SIV strains. The inability of SIV strains to use CXCR4 is unexpected since phylogenetic analysis suggests that HIV-1 and HIV-2 originated from simian viruses found in chimpanzees and sooty mangabeys respectively (21 22 Furthermore it has been demonstrated that various simian species from which SIVs have been isolated (chimpanzees rhesus macaques and sooty mangabeys) have CXCR4 genes that are highly homologous (>97%) to the human CXCR4 gene (7 9 30 Additionally it has been demonstrated that the rhesus macaque CXCR4 can function as a coreceptor for HIV-1 T-cell-tropic isolates when expressed on human cells (9 30 These findings suggest that the CXCR4 molecules expressed on simian cells should be capable of functioning as Rifampin a coreceptor for SIVs. The demonstration that rhesus macaque CXCR4 is functional on human cells together with the high homology of SIV isolates from sooty mangabeys to HIV-2 and the ability of HIV-2 to use CXCR4 led us to investigate the coreceptor utilization of primary SIV isolates derived from sooty mangabeys (SIVsm) a stumptail macaque (SIVstm) a mandrill (SIVmnd) and an African green monkey (SIVagm). We provide evidence that several primary SIV isolates are capable of using CXCR4. However in some cases the interaction between the SIV envelope and CXCR4 may occur in a manner slightly different than that reported for HIV-1 and CXCR4. The CXCR4 ligand SDF-1 a monoclonal antibody to CXCR4 and the CXCR4 antagonistic compounds T-22 and AMD3100 Rifampin had variable abilities to block the entry of some of the CXCR4-utilizing SIV strains at concentrations that completely blocked HIV-1 entry. Primary SIVs were isolated by cocultivation with either staphylococcal enterotoxin B-stimulated pigtail macaque (is confined to V1 and V4 Rifampin during progression to simian AIDS. J Virol. 1991;65:7025-7031. [PMC free article] [PubMed] 37 Owen S M Ellenberger D Rayfield M Wiktor S Michel P Grieco M H Gao F Hahn B H Lal R B. Genetically divergent strains of human immunodeficiency virus type 2 use multiple coreceptors for viral entry. J Virol. 1998;72:5425-5432. [PMC free article] [PubMed] 38 Reeves J D Hibbitts S Simmons G McKnight A Azevedo-Pereira J M Moniz-Pereira J Clapham P R. Primary human immunodeficiency virus type 2 (HIV-2) isolates infect CD4-negative cells via CCR5 and CXCR4: comparison with HIV-1 and simian immunodeficiency virus and relevance to cell tropism in vitro. J Virol. 1999;73:7795-7804. [PMC free article] [PubMed] 39 Saitou N Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987;4:406-425. [PubMed] 40 Saksena N K Wang B Novembre F J Bolton W Smit T K Lal R B. Species-specific changes in the CCR5 gene from African.