Modulation of stress protein (hsp27 and hsp70) expression in CD4+ lymphocytic cells following acute infection with human immunodeficiency virus type-1.
This study was designed to assess the impact of acute human immunodeficiency virus (HIV-1) infection on host intracellular expression of the heat shock family of stress proteins (hsps). Experimental conditions were established wherein CD4+ lymphocytic cell lines undergo a synchronous HIV-1 infection cycle. During the early phase of infection, HIV-1 mRNA expression was restricted to singly and multiply spliced subspecies, with no genomic viral RNA present until 30 hr following infection. In contrast, hsp27 and hsp70 mRNA transcription appeared as early as 3-8 hr following viral infection. No corresponding induction was observed in mock-infected cells. Notably, hsp27 and hsp70 mRNA transcripts were down-regulated by 24 hr, concomitant to the first appearance of full-length genomic HIV-1 mRNA. Hsp27 and hsp70 mRNA transcripts reemerged at end stages of the viral replicative cycle, coincident to virion release and CD4 cell death. Similarly, a transient induction of de novo hsp27 protein expression occurred between 12 and 24 hr. The generated hsp27 stress response was viral dose-related, suppressed by heat-inactivation of virus, and abrogated by neutralizing antibodies to HIV-1. Acute infection did not alter levels of hsp60, hsp70, and hsp90 protein synthesis. However, two-dimensional Western blot analysis did show the appearance of novel hsp70 homologues between 6 and 24 hr following infection. CEM.NKR, Jurkat, H9, and MT-2 cells showed similar patterns of viral-associated modulation of host hsp27 and hsp70 protein and RNA expression. Thus, host hsp27 and hsp70 stress pathways are selectively implicated in the HIV-1 viral life cycle.
Wainberg
Z
Z
McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Oliveira
M
M
Lerner
S
S
Tao
Y
Y
Brenner
B G
BG
D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006361:Heating; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D009500:Neutralization Tests; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger; D014407:Tumor Cells, Cultured; D000099190:MAP-Kinase-Activated Kinase 2
D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099190:MAP-Kinase-Activated Kinase 2