Modulation of human immunodeficiency virus type 1 infectivity through incorporation of tetraspanin proteins.
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.
Sato
Kei
K
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoinkawara-cho, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan.
Aoki
Jun
J
Misawa
Naoko
N
Daikoku
Eriko
E
Sano
Kouichi
K
Tanaka
Yuetsu
Y
Koyanagi
Yoshio
Y
D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002460:Cell Line; D015497:HIV-1 / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D059470:Tetraspanins; D014771:Virion / Q000737:chemistry*; D053586:Virus Internalization
D015703:Antigens, CD; D000954:Antigens, Surface; C554586:CD63 protein, human; C554798:CD81 protein, human; C497688:CD82 protein, human; C554869:CD9 protein, human; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010980:Platelet Membrane Glycoproteins; C404405:TSPAN7 protein, human; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; D059470:Tetraspanins; C074075:TM4SF1 protein, human