Previous Article | Next Article 
Journal of Virology, February 2001, p. 1672-1680, Vol. 75, No. 4
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.4.1672-1680.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Genetic and Functional Diversity of Human
Immunodeficiency Virus Type 1 Subtype B Nef Primary Isolates
John L.
Foster,1
Rene P.
Molina,1
Tianci
Luo,2
Vivek K.
Arora,1
Yaoxing
Huang,3
David D.
Ho,3 and
J. Victor
Garcia1,*
Department of Internal Medicine, Division of
Infectious Diseases, University of Texas Southwestern Medical Center
at Dallas, Dallas, Texas 753901;
Genetic Therapy, Inc., Gaithersburg, Maryland
208792; and Aaron Diamond AIDS
Research Center, Rockefeller University, New York, New York
100163
Received 28 August 2000/Accepted 9 November 2000
We have characterized the functional integrity of seven primary Nef
isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with
AIDS. One of the seven Nefs was defective for CD4 downregulation, two
others were defective for PAK-2 activation, and one Nef was defective
for PAK-2 activation and major histocompatibility complex (MHC) class I
downregulation. Five of the Nefs were tested and found to be functional
for the enhancement of virus particle infectivity. The structural basis
for each of the functional defects has been analyzed by constructing
a consensus nef, followed by mutational analysis of
the variant amino acid residues. Mutations A29V and F193I were
deleterious to CD4 downregulation and PAK-2 activation, respectively,
while S189R rendered Nef defective for both MHC class I downregulation
and PAK-2 activation. A search of the literature identified HIVs from
five patients with Nefs predominantly mutated at F193 and from one
patient with Nefs predominantly mutated at A29. A29 is highly conserved
in all HIV subtypes except for subtype E. F193 is conserved in subtype
B (and possibly in the closely related subtype D), but none of the
other HIV group M subtypes. Our results suggest that functional
distinctions may exist between HIV subtypes.
*
Corresponding author. Mailing address: Department of
Internal Medicine, Division of Infectious Diseases Y9.206, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd.,
Dallas, TX 75390-9113. Phone: (214) 648-9970. Fax: (214) 648-0231. Email: victor.garcia{at}UTsouthwestern.edu.
Journal of Virology, February 2001, p. 1672-1680, Vol. 75, No. 4
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.4.1672-1680.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Schindler, M., Rajan, D., Specht, A., Ritter, C., Pulkkinen, K., Saksela, K., Kirchhoff, F.
(2007). Association of Nef with p21-Activated Kinase 2 Is Dispensable for Efficient Human Immunodeficiency Virus Type 1 Replication and Cytopathicity in Ex Vivo-Infected Human Lymphoid Tissue. J. Virol.
81: 13005-13014
[Abstract]
[Full Text]
-
Priceputu, E., Hanna, Z., Hu, C., Simard, M.-C., Vincent, P., Wildum, S., Schindler, M., Kirchhoff, F., Jolicoeur, P.
(2007). Primary Human Immunodeficiency Virus Type 1 Nef Alleles Show Major Differences in Pathogenicity in Transgenic Mice. J. Virol.
81: 4677-4693
[Abstract]
[Full Text]
-
O'Neill, E., Baugh, L. L., Novitsky, V. A., Essex, M. E., Garcia, J. V.
(2006). Intra- and intersubtype alternative pak2-activating structural motifs of human immunodeficiency virus type 1 nef.. J. Virol.
80: 8824-8829
[Abstract]
[Full Text]
-
Vincent, P., Priceputu, E., Kay, D., Saksela, K., Jolicoeur, P., Hanna, Z.
(2006). Activation of p21-activated Kinase 2 and Its Association with Nef Are Conserved in Murine Cells but Are Not Sufficient to Induce an AIDS-like Disease in CD4C/HIV Transgenic Mice. J. Biol. Chem.
281: 6940-6954
[Abstract]
[Full Text]
-
Agopian, K., Wei, B. L., Garcia, J. V., Gabuzda, D.
(2006). A Hydrophobic Binding Surface on the Human Immunodeficiency Virus Type 1 Nef Core Is Critical for Association with p21-Activated Kinase 2. J. Virol.
80: 3050-3061
[Abstract]
[Full Text]
-
O'Neill, E., Kuo, L. S., Krisko, J. F., Tomchick, D. R., Garcia, J. V., Foster, J. L.
(2006). Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef. J. Virol.
80: 1311-1320
[Abstract]
[Full Text]
-
Wei, B. L., Arora, V. K., Raney, A., Kuo, L. S., Xiao, G.-H., O'Neill, E., Testa, J. R., Foster, J. L., Garcia, J. V.
(2005). Activation of p21-Activated Kinase 2 by Human Immunodeficiency Virus Type 1 Nef Induces Merlin Phosphorylation. J. Virol.
79: 14976-14980
[Abstract]
[Full Text]
-
Raney, A., Kuo, L. S., Baugh, L. L., Foster, J. L., Garcia, J. V.
(2005). Reconstitution and Molecular Analysis of an Active Human Immunodeficiency Virus Type 1 Nef/p21-Activated Kinase 2 Complex. J. Virol.
79: 12732-12741
[Abstract]
[Full Text]
-
Milicic, A., Price, D. A., Zimbwa, P., Booth, B. L., Brown, H. L., Easterbrook, P. J., Olsen, K., Robinson, N., Gileadi, U., Sewell, A. K., Cerundolo, V., Phillips, R. E.
(2005). CD8+ T Cell Epitope-Flanking Mutations Disrupt Proteasomal Processing of HIV-1 Nef. J. Immunol.
175: 4618-4626
[Abstract]
[Full Text]