This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01044-07v1 82/2/1021    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sato, K. Articles by Koyanagi, Y. Search for Related Content PubMed PubMed Citation Articles by Sato, K. Articles by Koyanagi, Y.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 1021-1033, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01044-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Modulation of Human Immunodeficiency Virus Type 1 Infectivity through Incorporation of Tetraspanin Proteins

Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan,¹ Department of Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Miyagi 980-8575, Japan,² Department of Preventive and Social Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan,³ Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan⁴

Received 14 May 2007/ Accepted 27 October 2007

Accumulating evidence indicates that human immunodeficiency virus type 1 (HIV-1) acquires various cellular membrane proteins in the lipid bilayer of the viral envelope membrane. Although some virion-incorporated cellular membrane proteins are known to potently affect HIV-1 infectivity, the virological functions of most virion-incorporated membrane proteins remain unclear. Among these host proteins, we found that CD63 was eliminated from the plasma membranes of HIV-1-producing T cells after activation, followed by a decrease in the amount of virion-incorporated CD63, and in contrast, an increase in the infectivity of the released virions. On the other hand, we found that CD63 at the cell surface was preferentially embedded on the membrane of released virions in an HIV-1 envelope protein (Env)-independent manner and that virion-incorporated CD63 had the potential to inhibit HIV-1 Env-mediated infection in a strain-specific manner at the postattachment entry step(s). In addition, these behaviors were commonly observed in other tetraspanin proteins, such as CD9, CD81, CD82, and CD231. However, L6 protein, whose topology is similar to that of tetraspanins but which does not belong to the tetraspanin superfamily, did not have the potential to prevent HIV-1 infection, despite its successful incorporation into the released particles. Taken together, these results suggest that tetraspanin proteins have the unique potential to modulate HIV-1 infectivity through incorporation into released HIV-1 particles, and our findings may provide a clue to undiscovered aspects of HIV-1 entry.

Published ahead of print on 7 November 2007.