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PMID: 15452228 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Repression of human T-cell leukemia virus type 1 and type 2 replication by a viral mRNA-encoded posttranscriptional regulator.

Journal of virology ·Vol. 78 ·No. 20 ·2004-10-00 ·Pages 11077-83

Younis I, Khair L, Dundr M, Lairmore MD, Franchini G, Green PL

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 are complex retroviruses that persist in the host, eventually causing leukemia and neurological disease in a small percentage of infected individuals. In addition to structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory (open reading frame I and II) proteins. The viral Tax and Rex proteins positively regulate virus production. Tax activates viral and cellular transcription to promote T-cell growth and, ultimately, malignant transformation. Rex acts posttranscriptionally to facilitate cytoplasmic expression of viral mRNAs that encode the structural and enzymatic gene products, thus positively controlling virion expression. Here, we report that both HTLV-1 and HTLV-2 have evolved accessory genes to encode proteins that act as negative regulators of both Tax and Rex. HTLV-1 p30(II) and the related HTLV-2 p28(II) inhibit virion production by binding to and retaining tax/rex mRNA in the nucleus. Reduction of viral replication in a cell carrying the provirus may allow escape from immune recognition in an infected individual. These data are consistent with the critical role of these proteins in viral persistence and pathogenesis in animal models of HTLV-1 and HTLV-2 infection.

MeSH Terms
Cell Line Down-Regulation Gene Expression Regulation, Viral Gene Products, rex/metabolism Gene Products, tax/metabolism Genes, pX Human T-lymphotropic virus 1/genetics,physiology Human T-lymphotropic virus 2/genetics,physiology Humans RNA, Messenger/metabolism RNA, Viral/metabolism Retroviridae Proteins/metabolism Virus Replication/drug effects
Chemicals
Gene Products, rex Gene Products, tax RNA, Messenger RNA, Viral Retroviridae Proteins tof protein, Human T-lymphotropic virus 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Younis Ihab
Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Rd., Columbus, OH 43210, USA.
Khair Lyne
Dundr Miroslav
Lairmore Michael D
Franchini Genoveffa
Green Patrick L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.78.20.11077-11083.2004
Published
2004-10-00
Pages
11077-83
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC521841
Subset
IM
Grants
NCI NIH HHS · CA 77556 · United States
NCI NIH HHS · CA 92009 · United States
NCI NIH HHS · P01 CA100730-01 · United States
NCI NIH HHS · R01 CA077556 · United States
NCI NIH HHS · R01 CA092009 · United States
External Links
PubMed source DOI: 10.1128/JVI.78.20.11077-11083.2004 PMC Full Text View journal details
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