HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 18, 15363-15375, May 3, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/18/15363    most recent M201479200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-F. Articles by Chen, S. S.-L. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-F. Articles by Chen, S. S.-L. Social Bookmarking                      What's this?

Effect of Point Mutations in the N Terminus of the Lentivirus Lytic Peptide-1 Sequence of Human Immunodeficiency Virus Type 1 Transmembrane Protein gp41 on Env Stability^*

Sheau-Fen Lee, Chiung-Yuan Ko, Chin-Tien Wang^§, and Steve S.-L. Chen^¶

From the  Division of Infectious Diseases, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, ^§ Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan, Republic of China

To understand the role of the lentivirus lytic peptide-1 region of the human immunodeficiency virus type 1 transmembrane glycoprotein (gp) 41 in viral infection, we examined the effects on virus replication of single amino acid deletions spanning this region in an infectious provirus of the HXB2 strain. Among the mutants analyzed, only the deletion of one of the two adjacent valine residues located at positions 832 and 833 (termed the 833 mutant for simplicity) greatly reduced the steady-state, cell-associated levels of the Env precursor and gp120, as opposed to the wild-type virus. The altered Env phenotype resulted in severely impaired virus infectivity and gp120 incorporation into this mutant virion. Analyses of additional mutants with deletions at Ile-830, Ala-836, and Ile-840 demonstrated that the 830 mutant exhibited the most significant inhibitory effect on Env steady-state expression. These results indicate that the N terminus of the lentivirus lytic peptide-1 region is critical for Env steady-state expression. Among the mutant viruses encoding Env proteins in which residues Val-832 and Val-833 were individually substituted by nonconserved amino acids Ala, Ser, or Pro, which were expected to disrupt the -helical structure in the increasingly severe manner of Pro > Ser > Ala, only the 833P mutant exhibited significantly reduced steady-state Env expression. Pulse labeling and pulse-chase studies demonstrated that the 830, 833, and 833P mutants of Env proteins degraded more rapidly in a time-dependent manner after biosynthesis than did the wild-type Env. The results indicate that residue 830 and 833 mutations are likely to induce a conformational change in Env that targets the mutant protein for cellular degradation. Our study has implications about the structural determinants located at the N terminus of the lentivirus lytic peptide-1 sequence of gp41 that affect the fate of Env in virus-infected cells.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				W.-E. Chan, C.-K. Chuang, S.-H. Yeh, M.-S. Chang, and S. S.-L. Chen Functional characterization of heptad repeat 1 and 2 mutants of the spike protein of severe acute respiratory syndrome coronavirus. J. Virol., April 1, 2006; 80(7): 3225 - 3237. [Abstract] [Full Text] [PDF]

				W.-E. Chan, H.-H. Lin, and S. S.-L. Chen Wild-Type-Like Viral Replication Potential of Human Immunodeficiency Virus Type 1 Envelope Mutants Lacking Palmitoylation Signals J. Virol., July 1, 2005; 79(13): 8374 - 8387. [Abstract] [Full Text] [PDF]

				W.-E. Chan, Y.-L. Wang, H.-H. Lin, and S. S.-L. Chen Effect of Extension of the Cytoplasmic Domain of Human Immunodeficiency Type 1 Virus Transmembrane Protein gp41 on Virus Replication J. Virol., May 15, 2004; 78(10): 5157 - 5169. [Abstract] [Full Text] [PDF]

				V. Kalia, S. Sarkar, P. Gupta, and R. C. Montelaro Rational Site-Directed Mutations of the LLP-1 and LLP-2 Lentivirus Lytic Peptide Domains in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41 Indicate Common Functions in Cell-Cell Fusion but Distinct Roles in Virion Envelope Incorporation J. Virol., March 15, 2003; 77(6): 3634 - 3646. [Abstract] [Full Text] [PDF]