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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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