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Journal of Virology, April 1999, p. 2675-2681, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vif Protein

James H. M. Simon,1 Ann M. Sheehy,2 Elise A. Carpenter,2 Ron A. M. Fouchier,2 and Michael H. Malim1,2,3,*

Howard Hughes Medical Institute2 and Departments of Microbiology1 and Medicine,3 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148

Received 30 July 1998/Accepted 9 December 1998

Lentivirus Vif proteins are potent regulators of virus infectivity. However, relatively little is known about the functional domains, peptide motifs, or residues of any Vif protein. In this report, we present the first extensive mutagenesis analysis of the 192-amino-acid human immunodeficiency virus type 1 (HIV-1) Vif protein. A large number of scanning missense (mostly alanine substitution) and deletion mutations were introduced into the HIV-1HXB3 vif gene, and the resulting proteins were evaluated for the induction of virus infectivity as well as subcellular localization. The results show that amino acids dispersed throughout Vif's linear sequence are important for function. However, because many of the inactive proteins also appear to be mislocalized, we suggest that many of them may actually be misfolded rather lacking an intracellular targeting signal. Interestingly, disruptions within an internal region spanning residues 114 to 146 give rise to mutant proteins that either retain function or are inactive but are not substantially mislocalized. We therefore speculate that this region, which harbors two essential cysteine residues and one essential serine residue, may contain aspects of a putative Vif effector domain.

* Corresponding author. Mailing address: Departments of Microbiology and Medicine, University of Pennsylvania School of Medicine, Clinical Research Bldg., Room 347B, 415 Curie Blvd., Philadelphia, PA 19104-6148. Phone: (215) 573-3493. Fax: (215) 573-2172. E-mail: malim{at}mail.med.upenn.edu.

Journal of Virology, April 1999, p. 2675-2681, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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