Arginine insertion and loss of N-linked glycosylation site in HIV-1 envelope V3 region confer CXCR4-tropism.
The third variable region (V3) of HIV-1 envelope glycoprotein gp120 plays a key role in determination of viral coreceptor usage (tropism). However, which combinations of mutations in V3 confer a tropism shift is still unclear. A unique pattern of mutations in antiretroviral therapy-naive HIV-1 patient was observed associated with the HIV-1 tropism shift CCR5 to CXCR4. The insertion of arginine at position 11 and the loss of the N-linked glycosylation site were indispensable for acquiring pure CXCR4-tropism, which were confirmed by cell-cell fusion assay and phenotype analysis of recombinant HIV-1 variants. The same pattern of mutations in V3 and the associated tropism shift were identified in two of 53 other patients (3.8%) with CD4(+) cell count <200/mm(3). The combination of arginine insertion and loss of N-linked glycosylation site usually confers CXCR4-tropism. Awareness of this rule will help to confirm the tropism prediction from V3 sequences by conventional rules.
AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Kiyoto
K
Tsuchiya
Hirotaka
H
Ode
Tsunefusa
T
Hayashida
Junko
J
Kakizawa
Hironori
H
Sato
Shinichi
S
Oka
Hiroyuki
H
Gatanaga
D001120:Arginine / Q000235:genetics*; D001483:Base Sequence; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000235:genetics*; D056189:Viral Tropism / Q000235:genetics*
C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1; D001120:Arginine