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Journal of Virology, April 2001, p. 3462-3468, Vol. 75, No. 7
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3462-3468.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Naturally Occurring Deletional Mutation in the C-Terminal
Cytoplasmic Tail of CCR5 Affects Surface Trafficking of
CCR5
Tatsuo
Shioda,1,*
Emi E.
Nakayama,1
Yuetsu
Tanaka,2
Xiaomi
Xin,3
Huanliang
Liu,1
Ai
Kawana-Tachikawa,3
Atsushi
Kato,4
Yuko
Sakai,3
Yoshiyuki
Nagai,4 and
Aikichi
Iwamoto3
Research Institute for Microbial Diseases,
Osaka University, Osaka,1 Ryukyu
University, Okinawa,2 and Institute
of Medical Science, University of Tokyo,3 and
National Institute of Infectious
Diseases,4 Tokyo, Japan
Received 20 September 2000/Accepted 22 December 2000
CCR5 is an essential coreceptor for the cellular entry of R5
strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(
) is
a single-nucleotide deletion mutation which is observed exclusively in
Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221-222, 1997).
This mutant gene produces a CCR5 which lacks the entire C-terminal
cytoplasmic tail. To assess the effect of CCR5-893(
) on HIV-1
infection, we generated a recombinant Sendai virus expressing the
mutant CCR5 and compared its HIV-1 coreceptor activity with that of
wild-type CCR5. Although the mutant CCR5 has intact extracellular domains, its coreceptor activity was much less than that of wild-type CCR5. Flow cytometric analyses and confocal microscopic observation of
cells expressing the mutant CCR5 revealed that surface CCR5 levels were
greatly reduced in these cells, while cytoplasmic CCR5 levels of the
mutant CCR5 were comparable to that of the wild type. Peripheral blood
CD4+ T cells obtained from individuals heterozygous for
this allele expressed very low levels of CCR5. These data suggest that
the CCR5-893(
) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1
transmission and disease progression.
*
Corresponding author. Mailing address: Department of
Viral Infections, Research Institute for Microbial Diseases, Osaka
University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone:
81-6-6879-8346. Fax: 81-6-6879-8347. E-mail:
shioda{at}biken.osaka-u.ac.jp.
Journal of Virology, April 2001, p. 3462-3468, Vol. 75, No. 7
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3462-3468.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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