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Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta GA, USA
Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA
Depratment of Pediatrics, Morehouse School of Medicine, Atlanta, GA, USA
Gladstone Institute of Virology and Immunology, San Francisco, CA, USA
Present address: Dupont Pharmaceuticals Company, Experimental Station E400/6220D, P.O. Box 80400, Wilmington DE, USA
* Author to whom correspondence should be addressed.
Received: 7 June 2002; Accepted: 31 October 2002 / Published: 31 October 2002
Abstract: Unusual HIV-1 nef alleles were isolated from a woman and her vertically infected child. Both patients eventually progressed to develop AIDS. The child died at age 6.5 years, while the mother is currently alive, 13 years since her diagnosis with HIV-1. Predicted amino acid sequences of both mother and child Nefs diverged from the HIV-1 clade B consensus. In particular, they exhibited two separate 5-amino acid deletions bracketing a Cterminal dileucine regulatory motif and Trp-Gly mutations at the site for cleavage by the HIV-1 protease. The child’s Nef showed a modest ability to enhance HIV-1 infectivity in MAGI cells, whereas the mother’s Nef did not alter HIV-1 infectivity in the assay. Both Nefs were partially functional for CD4 down-regulation. The child’s Nef was fully functional for MHC-1 down-regulation, while the maternal Nef was non-functional. To our knowledge this study is the first to describe a functional divergence between Nef alleles in a case of mother-to-child HIV-1 transmission.
Keywords: HIV-1; Nef; in vitro; CD4; MHC; infectivity
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Roth, W.W.; Khan, M.; Geleziunas, R.; Stringer, H.G., Jr.; Zuberi, J.A.; Greene, W.C.; Powell, M.; Bond, V.C. Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair. Int. J. Mol. Sci. 2002, 3, 1058-1072.
Roth WW, Khan M, Geleziunas R, Stringer HG, Jr, Zuberi JA, Greene WC, Powell M, Bond VC. Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair. International Journal of Molecular Sciences. 2002; 3(10):1058-1072.
Roth, William W.; Khan, Mafhuz; Geleziunas, Romas; Stringer, Harold G., Jr.; Zuberi, Jalal A.; Greene, Warner C.; Powell, Michael; Bond, Vincent C. 2002. "Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair." Int. J. Mol. Sci. 3, no. 10: 1058-1072.