Genetic variability of HIV-1 protease from Nigeria and correlation with protease inhibitors drug resistance

被引:13
|
作者
Vicente, ACP
Agwale, SM
Otsuki, K
Njouku, OM
Jelpe, D
Idoko, JA
Caride, E
Brindeiro, RM
Tanuri, A
机构
[1] Inst Oswaldo Cruz, Dept Genet, BR-21045900 Rio De Janeiro, Brazil
[2] Univ Jos, Dept Zool, Lab Leishmaniasis & AIDS, Jos, Nigeria
[3] Plateau Hosp, AIDS Res Ctr, ISCC World Lab, Jos, Nigeria
[4] Univ Jos, Teaching Hosp, Dept Med, Jos, Nigeria
[5] Univ Fed Rio de Janeiro, Dept Genet, BR-21941 Rio De Janeiro, Brazil
关键词
HIV-1; protease; subtype; anti-retroviral therapy; recombinant; mutation;
D O I
10.1023/A:1008123508416
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In Nigeria, the most populous country in Africa, the characterization of HIV-1 strains has been limited. In this study we evaluated the genetic diversity of the protease coding region, one of the anti-retroviral therapy target, and investigated the presence of mutations related to resistance to HIV protease inhibitors. We analyzed samples collected during 1996 and all patients were anti-retroviral drug naives. Ten samples were evaluated by sequencing of the protease gene. The majority, 80%, were classified as subtype A and the two others were unclassified-divergent strains, something in between A and G subtypes. The gag region from these outliners were sequenced and the phylogenetic analysis classified them as subtype G. The protease amino acid consensus sequence of the Nigerian subtype A are in complete agreement with the consensus A differing from the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I, R41K, P63L, H69K and L89M). The secondary substitutions associated with protease inhibitor resistance were observed in all Nigerian sequences at the positions L10V, M36I and L89M. The majority of sequence variation was concentrated in the interval between aminoacids 70-90 where the protease substrate binding region is located.
引用
收藏
页码:181 / 186
页数:6
相关论文
共 50 条
  • [21] A cell-free enzymatic activity assay for the evaluation of HIV-1 drug resistance to protease inhibitors
    Matsunaga, Satoko
    Masaoka, Takashi
    Sawasaki, Tatsuya
    Morishita, Ryo
    Iwatani, Yasumasa
    Tatsumi, Masashi
    Endo, Yaeta
    Yamamoto, Naoki
    Sugiura, Wataru
    Ryo, Akihide
    FRONTIERS IN MICROBIOLOGY, 2015, 6
  • [22] Drug design: New inhibitors for HIV-1 protease based on Nelfinavir as lead
    Perez, M. A. S.
    Fernandes, P. A.
    Ramos, M. J.
    JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2007, 26 (03) : 634 - 642
  • [23] Genetic Diversity and Drug Resistance Mutations in Reverse Transcriptase and Protease Genes of HIV-1 Isolates from Southwestern Siberia
    Rudometova, Nadezhda B.
    Shcherbakova, Nadezhda S.
    Shcherbakov, Dmitry N.
    Mishenova, Elena V.
    Delgado, Elena
    Ilyichev, Alexander A.
    Karpenko, Larisa I.
    Thomson, Michael M.
    AIDS RESEARCH AND HUMAN RETROVIRUSES, 2021, 37 (09) : 716 - 723
  • [24] HIV-1 protease inhibitors: A comparative QSAR analysis
    Kurup, A
    Mekapati, SB
    Garg, R
    Hansch, C
    CURRENT MEDICINAL CHEMISTRY, 2003, 10 (17) : 1679 - 1688
  • [25] Prenylisoflavonoids from Erythrina senegalensis as Novel HIV-1 Protease Inhibitors
    Lee, JiSuk
    Oh, Won Keun
    Ahn, Jong Seog
    Kim, Yong Hae
    Mbafor, J. Tanyi
    Wandji, Jean
    Fomum, Z. Tanee
    PLANTA MEDICA, 2009, 75 (03) : 268 - 270
  • [26] Phenanthridine derivatives as potential HIV-1 protease inhibitors
    Ershov, Pavel V.
    Mezentsev, Yuri V.
    Kaluzhskiy, Leonid A.
    Ivanov, Alexis S.
    BIOMEDICAL REPORTS, 2020, 13 (06) : 1 - 7
  • [27] CHARACTERIZATION OF DYNAMIC STATE INHIBITORS OF HIV-1 PROTEASE
    VAILLANCOURT, M
    COHEN, E
    SAUVE, G
    JOURNAL OF ENZYME INHIBITION, 1995, 9 (03): : 217 - 233
  • [28] Molecular dynamics studies on HIV-1 protease drug resistance and folding pathways
    Cecconi, F
    Micheletti, C
    Carloni, P
    Maritan, A
    PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2001, 43 (04): : 365 - 372
  • [29] Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3
    Heaslet, H
    Kutilek, V
    Morris, GM
    Lin, YC
    Elder, JH
    Torbett, BE
    Stout, CD
    JOURNAL OF MOLECULAR BIOLOGY, 2006, 356 (04) : 967 - 981
  • [30] Energetic basis for drug resistance of HIV-1 protease mutants against amprenavir
    Kar, Parimal
    Knecht, Volker
    JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2012, 26 (02) : 215 - 232