Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools.
Human immunodeficiency virus type 1 (HIV-1) replication is shown to be sensitive to the intracellular concentration of deoxynucleoside triphosphate substrates. Addition of thymidine to established cell lines resulted in a dramatic reduction of virus production. The effect could be substantially alleviated by addition of deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3. Hydroxyurea treatment abolished HIV-1 replication in peripheral blood mononuclear cells and could be reversed by deoxyadenosine. These data show that HIV-1 replication occurs under suboptimal DNA precursor conditions.
Meyerhans
A
A
Abteilung Virologie, Universität Freiburg, Germany.
Vartanian
J P
JP
Hultgren
C
C
Plikat
U
U
Karlsson
A
A
Wang
L
L
Eriksson
S
S
Wain-Hobson
S
S
D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003841:Deoxycytidine / Q000494:pharmacology*; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D011533:Proviruses / Q000235:genetics; D013936:Thymidine / Q000494:pharmacology*; D013942:Thymine Nucleotides / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D003838:Deoxyadenine Nucleotides; D003845:Deoxycytosine Nucleotides; D003848:Deoxyguanine Nucleotides; D013942:Thymine Nucleotides; D003841:Deoxycytidine; C024107:2'-deoxycytidine 5'-triphosphate; C029603:deoxyguanosine triphosphate; C024157:thymidine 5'-triphosphate; D013936:Thymidine