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J. Biol. Chem., Vol. 281, Issue 7, 3964-3971, February 17, 2006
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1
From the
HIV Drug Resistance Program, NCI-Frederick, Frederick, Maryland 21702,
Department of Biochemistry, Medical University of Debrecen, H-4012 Debrecen, Hungary, and ¶Basic Research Program, SAIC-Frederick, Frederick, Maryland 21702
It is not known whether the low infectivity and low virion-associated polymerase activity of human T-cell lymphotropic virus type-1 (HTLV-1) are due to the quantity or quality of the reverse transcriptase (RT), because the protein has not yet been fully characterized. We have developed anti-RT antibodies and constructed HTLV-1 expression plasmids that express truncated or hemagglutinin-tagged Pol polyproteins to examine the maturation and composition of HTLV-1 RT. We detected virion-associated proteins corresponding to RT-integrase (IN) (pr98) and RT (p62) as well as smaller proteins containing the polymerase (p49) or RNase H domains. We have identified the amino acid sequences in the Pol polyprotein that are cleaved by HTLV-1 protease to yield RT and IN. We have also identified the cleavage sites within RT that give rise to the p49 polymerase fragment. Immunoprecipitation of an epitope-tagged p62 subunit coprecipitated p49, indicating that the HTLV-1 RT complex can exist as a p62/p49 heterodimer analogous to the RT of HIV-1 (p66/p51).
Received for publication, July 14, 2005 , and in revised form, December 12, 2005.
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: National Cancer Institute, P.O. Box B, Bldg. 535/134, Frederick, MD 21702. Tel.: 301-846-5611; Fax: 301-846-6863; E-mail: derse{at}ncifcrf.gov.
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