HIV-1 glycoprotein 41 ectodomain induces activation of the CD74 protein-mediated extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to enhance viral infection.
Besides mediating the viral entry process, the human immunodeficiency virus (HIV-1) envelope protein gp41 can bind to many host cell components and regulate cell functions. Using a yeast two-hybrid system, we screened a human bone marrow cDNA library and identified a novel gp41-binding protein, CD74 (the MHC class II-associated invariant chain). Here, we report possible biological effects mediated by interaction between gp41 and CD74. We found that HIV-1 gp41 could bind directly to host CD74 in HIV-1-infected cells, and the peptide 6358 derived from gp41 loop region (aa 597-611) could effectively block the gp41-CD74 interaction. As a result of this binding, recombinant soluble gp41 and gp41 peptide 6358 activated the CD74-mediated ERK/MAPK pathway and significantly enhanced HIV-1 infection in vitro. Conversely, the enhancing effect could be suppressed by the recombinant CD74 extracellular domain. These results reveal a novel mechanism underlying gp41 mediation of HIV-1 infection and replication.
Laboratory of Immunology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Chang
C
Zhou
Lu
L
Lu
Suiyi
S
Tan
Shibo
S
Jiang
Ying-Hua
YH
Chen
D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D000944:Antigens, Differentiation, B-Lymphocyte; D015700:HIV Envelope Protein gp41; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1; C045084:invariant chain