Different susceptibility of human immunodeficiency virus type 1 to Env gp41-derived synthetic peptides corresponding to the C-terminal heptad repeat region.
Two functional domains, alpha-helical heptad repeat 1 (HR-1) and HR-2, located in the N-terminal and C-terminal regions of human immunodeficiency virus type 1 (HIV-1) Env gp41, respectively, play an important role in the fusion process. Synthetic 34-amino-acid peptide that contains the HR-2 region, named C34, has been shown to inhibit the HIV-1 fusion process. Here, we prepared six representative peptides (C34-B1, -B2, -A, -C1, -C2, and -E from subtypes B, A, C, and E, respectively) according to the sequences from the HIV sequence database of Los Alamos. All the C34 peptides had lower ability to inhibit the primary isolates (subtypes B and CRF01_AE) than subtype B laboratory strain LAI. On the other hand, the L-2 cell clone, isolated from persistently LAI-infected MT-4 cells (MT-4/LAI), showed unique C34 peptide sensitivities. L-2 virus has the same sequences at HR-1 and HR-2 regions as LAI, but showed higher syncytia formation activity than LAI. Interestingly, the sensitivity of L-2 was higher to C34-B2 and -A but slightly lower to C34-C1 at higher concentrations than MT-4/LAI, while C34-B1, -C2, and -E showed similar activity against both viruses. Thus, in addition to the sequences of the C34 peptide as well as of the HR-1 and HR-2 regions in target viruses used for fusion assays, the fusion inhibitory activities of C34 peptides seem to be affected by viral factor(s) other than the gp41 alpha-helical heptad repeats.
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Panasda Isarangkura
PI
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Li
Gui-Mei
GM
Warachit
Jiranan
J
Iwabu
Yukie
Y
Tsuji
Shoutaro
S
Auwanit
Wattana
W
Yamamoto
Daisuke
D
Goto
Toshiyuki
T
Hayashi
Yoshio
Y
Kiso
Yoshiaki
Y
Ikuta
Kazuyoshi
K
D000595:Amino Acid Sequence; D002460:Cell Line; D014644:Genetic Variation; D015726:Giant Cells / Q000187:drug effects / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010802:Phylogeny
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C407149:peptide C34