Details

Autor(en) / Beteiligte

• Julias, John G
• Boyer, Paul L
• McWilliams, Mary Jane
• Alvord, W.Gregory
• Hughes, Stephen H

Titel

Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis

Ist Teil von

• Virology (New York, N.Y.), 2004-04, Vol.322 (1), p.13-21

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Methionine at position 184 of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) was changed to valine, isoleucine, threonine, or alanine in an HIV-1-based vector. The vectors were analyzed for replication capacity and for resistance to the nucleoside analog 2′,3′-dideoxy-3′thiacytidine (3TC) using a single-cycle assay. Viruses containing the valine or isoleucine mutations were highly resistant to 3TC and replicated almost as well as the wild-type virus. The virus containing the threonine mutation was resistant to 3TC, but replicated about 30% as well as the wild-type. The alanine mutation conferred partial resistance to 3TC, but replicated poorly. The amounts of viral DNA synthesized decreased in 3TC-treated cells when the cells were infected with wild-type virus and the M184A mutant. The effect of these mutations on the generation of the ends of the linear viral DNA was determined using the sequence of the 2-LTR circle junctions. The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT.