AEGiS-12IAC: Coreceptor use and MT2 tropism of HIV-1 chimeric clones having envelope V3 loop of HIV-1 subtype E.

12th International AIDS Conference


Geneva, Switzerland - June 28-July 3, 1998

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Coreceptor use and MT2 tropism of HIV-1 chimeric clones having envelope V3 loop of HIV-1 subtype E.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:5 (abstract no. 11113)

Sato H, Kato KK, Kodaka NK, Takebe YT
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

OBJECTIVE: HIV-1 subtype E has phylogenetically distinct class of envelope sequence from HIV-1 subtype B, showing about 60% identity in amino acids of envelope V3 loop. We examined whether the subtype E V3 loop has a capacity to specify coreceptor use and MT2 tropism of virus in context of subtype B background.

METHODS: V3 loop coding region of an infectious molecular clone of HIV-1 subtype B (LAI) was replaced precisely by that of HIV-1 subtype E from nonsyncytium-inducing (NSI) variants (NH2 and TH09) or from syncytium-inducing (SI) variants (NH1 and KH005). Coreceptor use of the chimeric viruses was assessed by infectivity on HOS-CD4 cells expressing various chemokine receptors. Site-specific mutagenesis was used to determine minimum requirements in the subtype E V3 loop for specifying viral phenotypes.

RESULTS: HIV-1LAI-NH2V3 and HIV-1LAI-TH09V3 replicated on HOS-CD4-CCR5, whereas HIV-1LAI, HIV-1LAI-NH1V3 and HIV-1LAI-KH005V3 grew preferentially on cells expressing CXCR4. HIV-1LAI-NH2V3 and HIV-1LAI-TH09V3 were unable to replicate on MT2 cells, whereas 1LAI, HIV-1LAI-NH1V3 and HIV-1LAI-KH005V3 grew and induced syncytia. Mutants with at least two naturally-occurring basic substitutions found in a SI variant grew efficiently on HOS-CD4-CXCR4, whereas acquisition of MT2 tropism required three basic substitutions (positions 8, 11 and 18) in the NSI V3.

CONCLUSION: The data indicate the HIV-1 subtype E V3 loop can specify coreceptor use and MT 2 tropism in context of subtype B envelope protein and that combination of basic substitutions similar but not identical to subtype B can generate CXCR4 preference for the chimeric virus.

Keywords: AEGIS, HIV-1, Tropism, HIV Infections, Antigens, CD4, Giant Cells, CD4-Positive T-Lymphocytes, HIV Seropositivity, Variation (Genetics), immunology, genetics, ICA12KWDaegis,hiv-1,tropism,hivinfections,antigens,cd4,giantcells,cd4-positivet-lymphocytes,hivseropositivity,variation(genetics),immunology,genetics,ica12
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