Comparative Fitness of Multi-Dideoxynucleoside-Resistant Human Immunodeficiency Virus Type 1 (HIV-1) in an In Vitro Competitive HIV-1 Replication Assay

• DOI: 10.1128/jvi.73.7.5356-5363.1999
• Publication Date: 2019-12-31T18:32:26Z
• Authors: Pope Kosalaraksa; Mark F. Kavlick; Victor Maroun; Richard Le; Hiroaki Mitsuya
• Keywords: Didanosine; clone (Java method)

ABSTRACT We examined whether human immunodeficiency virus type 1 (HIV-1) fitness was altered upon the acquisition of a set or subset five mutations (A62V, V75I, F77L, F116Y, and Q151M) in pol gene, which confers resistance to multiple dideoxynucleosides (MDR), as well zidovudine resistance-associated mutation T215Y, using competitive HIV-1 replication assay setting an HXB2D genetic background. Target H9 cells were exposed 50:50 mixture paired infectious molecular clones, culture supernatant transmitted new cultures every 7 10 days. The polymerase-encoding region sequenced at various time points, relative proportion two viral populations determined. In absence drugs, comparative order for replicative 62/75/77/116/151 > 77/116/151 151 wild-type (HIV-1 wt ) 75/77/116/151 151/215 215 . presence didanosine, 215S(TCC) , putative intermediate clone replicated comparably while intermediates [HIV-1 151L(CTG) 151K(AAG) ] much less efficiently than suggesting that develop, base substitutions are likely occur concurrently within short interval. These data may illustrate basis by emerges frequently present also demonstrate several MDR variants more fit drugs drug pressure critical variates fitness.