AEGiS-13IAC: Non-reciprocal interaction between HIV-1 and HIV-2 Cross-packaging and derivation of lentiviral vectors for gene therapy.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Non-reciprocal interaction between HIV-1 and HIV-2 Cross-packaging and derivation of lentiviral vectors for gene therapy.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA169)

Arya S, D'Costa J, Davis - Warren A, Brown H
S. Arya, National Institutes of Health, National Cancer Institute #37 - 5 E 08, Bethesda MD 20892, United States, Tel.: +301 496 48 90, Fax: +301 496 58 39, E-mail: aryas@dc37a.nci.nih.gov

BACKGROUND: Though similar in over-all genomic structure, HIV-1 and HIV-2 differ from each other in many aspects of their natural history, transmission dynamics, and pathogenic potential, with HIV-2 generally being less pathogenic than HIV-1. Previous studies have shown a non-reciprocal interaction between HIV-1 and HIV-2 at the level of transactivation. We have proposed that this is determined in part by the structure of the their LTRs and Tats. We have now made similar observations for encapsidation.

METHODS: Encapsidation of HIV-1 and HIV-2 RNA by HIV-1 and HIV-2 packaging machinery was determined by measuring RNA content of the particles pseudotyped with VSV-G. Using indicator GFP and anti-HIV chemokine RANTES genes as transgenes, self- and cross-packaging was further evaluated by titerating the vectors for tranduction of a number of human cells. Results and

CONCLUSIONS: HIV-1 packaging machinery encapsidated HIV-1 and HIV-2 RNA to similar extent. About 20-30% of the vector RNA in the cell was encapsidated into particles. In contrast, HIV-2 packaging machinery was more selective. While it packaged HIV-2 RNA to roughly the extent as HIV-1, its packaging of HIV-1 RNA was 10-30-folds less efficient. This suggests that HIV-2 may yield a better quality vector than HIV-1. We propose that the non-reciprocal packaging has a similar basis as the previously observed non-reciprocal transactivation. It is determined in part by the leader sequence of the two viruses, which are quite dissimilar. Studies with chimera of the leaders and nucleocapsid proteins should provide additional insights into the mechanism of RNA encapsidation and virus assembly. These results are important for the development of lentiviral vectors derived from HIV-1 and HIV-2, particularly those designed for gene therapy of HIV infection and AIDS.

Keywords: AEGIS, HIV-2, HIV-1, Gene Therapy, Virus Assembly, HIV Infections, Transgenes, Human, virology, genetics
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