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Journal of Virology, June 2000, p. 5075-5082, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Simian Immunodeficiency Virus Utilizes Human and Sooty
Mangabey but Not Rhesus Macaque STRL33 for Efficient
Entry
Stefan
Pöhlmann,1
Benhur
Lee,2
Silke
Meister,1
Mandy
Krumbiegel,1
George
Leslie,2
Robert W.
Doms,2 and
Frank
Kirchhoff1,*
Institute for Clinical and Molecular
Virology, University of Erlangen-Nürnberg, 91054 Erlangen,
Germany,1 and Department of
Pathology and Laboratory Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 191042
Received 5 January 2000/Accepted 7 March 2000
It has been established that many simian immunodeficiency virus
(SIV) isolates utilize the orphan receptors GPR15 and STRL33 about as
efficiently as the chemokine receptor CCR5 for entry into target cells.
Most studies were performed, however, with coreceptors of human
origin. We found that SIV from captive rhesus macaques (SIVmac) can
utilize both human and simian CCR5 and GPR15 with comparable
efficiencies. Strikingly, however, only human STRL33
(huSTRL33), not rhesus macaque STRL33 (rhSTRL33), functioned efficiently as an entry cofactor for a variety of isolates of SIVmac
and SIV from sooty mangabeys. A single amino acid substitution of S30R in huSTRL33 impaired coreceptor activity, and the reverse change in rhSTRL33 greatly increased coreceptor activity. In
comparison, species-specific sequence variations in N-terminal
tyrosines in STRL33 had only moderate effects on SIV entry. These
results show that a serine residue located just outside of the cellular
membrane in the N terminus of STRL33 is critical for SIV coreceptor
function. Interestingly, STRL33 derived from sooty mangabeys, a
natural host of SIV, also contained a serine at the corresponding
position and was used efficiently as an entry cofactor. These results
suggest that STRL33 is not a relevant coreceptor in the
SIV/macaque model but may play a role in SIV replication and
transmission in naturally infected sooty mangabeys.
*
Corresponding author. Mailing address: Institute for
Clinical and Molecular Virology, University of Erlangen-Nürnberg,
Schlossgarten 4, 91054 Erlangen, Germany. Phone: 49-9131-852-6483. Fax:
49-9131-85-1002. E-mail:
fkkirchh{at}viro.med.uni-erlangen.de.
Journal of Virology, June 2000, p. 5075-5082, Vol. 74, No. 11
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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