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Journal of Virology, July 2001, p. 6601-6608, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6601-6608.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Nef from Human Immunodeficiency Virus Type 1_F12 Inhibits Viral Production and Infectivity

Oliver T. Fackler,^1,2 Paola d'Aloja,^3,4 Andreas S. Baur,³ Maurizio Federico,⁴ and B. Matija Peterlin^1,*

Departments of Medicine, Microbiology, and Immunology, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California 94143-0703¹; Institute for Hygiene, Department of Virology, University of Heidelberg, D-69120 Heidelberg,² and Department of Dermatology, University of Erlangen, D-91052 Erlangen,³ Germany; and Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy⁴

Received 20 November 2000/Accepted 13 April 2001

Human immunodeficiency virus type 1_F12 (HIV-1_F12) interferes with the replication of other strains of HIV. Its accessory protein, Nef, is sufficient for this phenotype, where the production and infectivity of HIV are impaired significantly. The analysis of three rare mutations in this Nef protein revealed that these effects could be separated genetically. Moreover, the defect in virus production correlated with the lack of processing of the p55^Gag precursor in the presence of Nef from HIV-1_F12. Importantly, the introduction of one of these mutations (E177G) into Nef from HIV-1_NL4-3 also created a dominant-negative Nef protein. Effects of Nef from HIV-1_F12 on virus production and Gag processing correlated with its altered subcellular distribution. Moreover, the association with two new cellular proteins with molecular masses of 74 and 75 kDa, which do not interact with other Nef proteins, correlated with the decreased virion infectivity. The identification of a dominant-negative protein for the production and infectivity of HIV suggests that Nef plays an active role at this stage of the viral replicative cycle.

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^* Corresponding author. Mailing address: UCSF Mt. Zion Cancer Center, Room N226, 2340 Sutter St., San Francisco, CA 94115. Phone: (415) 502-1905. Fax: (415) 502-1901. E-mail: matija{at}itsa.ucsf.edu.

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Journal of Virology, July 2001, p. 6601-6608, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6601-6608.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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