The role of lysine residue at amino acid position 165 of human immunodeficiency virus type 1 CRF01_AE Gag in reducing viral drug susceptibility to protease inhibitors.
Recombinant human immunodeficiency virus type 1 (HIV-1) containing a CRF01_AE Gag, AE-Gag62, was significantly less susceptible to protease inhibitors (PIs) than the subtype B reference strain, NL4-3; therefore, the mechanism of how AE-Gag62 reduced viral drug susceptibility to PIs was studied in this report. The results showed that the lysine residue at amino acid position 165 (K165) of AE-Gag62 played a role in reducing the drug susceptibility of the recombinant virus to PIs. In addition, K165 potentially appears more frequently in CRF01_AE viruses than in the viruses of other major HIV-1 subtypes. Although K165 had no effect on the extent of recombinant protease-mediated in vitro Gag cleavage, it enhanced the incorporation of the Gag-Pol precursor protein, p160, into virions. Taken together, these results suggest that K165 of CRF01_AE Gag affects the regulation of virion assembly or maturation, and reduces viral drug susceptibility to PIs.
Kameoka
Masanori
M
Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Nonthaburi 11000, Thailand. mkameoka@biken.osaka-u.ac.jp
Isarangkura-na-Ayuthaya
Panasda
P
Kameoka
Yoko
Y
Sapsutthipas
Sompong
S
Soonthornsata
Bongkot
B
Nakamura
Shota
S
Tokunaga
Kenzo
K
Sawanpanyalert
Pathom
P
Ikuta
Kazuyoshi
K
Auwanit
Wattana
W
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D008239:Lysine