Synonymous mutations in stem-loop III of Rev responsive elements enhance HIV-1 replication impaired by primary mutations for resistance to enfuvirtide.
Primary mutations in HIV-1 that are directly involved in the resistance to enfuvirtide have been well documented. However, secondary mutations that are associated with primary mutations and contribute little to the resistance still remain to be elucidated. This study reveals that synonymous mutations at gp41 Q41 (CAG to CAA) or L44 (UUG to CUG) act as secondary mutations. Complementary mutations in the nucleotide level are located in the Rev responsive element (RRE) of the HIV-1 RNA-genome and maintain the replication kinetics of HIV-1 through increasing the structural stability of stem-loop III in the RRE. Therefore, synonymous mutations in the gp41/RRE sequence improve the viral replication impaired by the primary mutations and play a key role as secondary (complementary) mutations.
Ueno
Mariko
M
Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Kodama
Eiichi N
EN
Shimura
Kazuya
K
Sakurai
Yasuteru
Y
Kajiwara
Keiko
K
Sakagami
Yasuko
Y
Oishi
Shinya
S
Fujii
Nobutaka
N
Matsuoka
Masao
M
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D017354:Point Mutation; D014779:Virus Replication / Q000187:drug effects; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics*
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D054321:rev Gene Products, Human Immunodeficiency Virus; D000077560:Enfuvirtide