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Journal of Virology, January 2003, p. 989-998, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.989-998.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Increased Mucosal Transmission but Not Enhanced Pathogenicity of the CCR5-Tropic, Simian AIDS-Inducing Simian/Human Immunodeficiency Virus SHIV_SF162P3 Maps to Envelope gp120

Mayla Hsu,¹ Janet M. Harouse,¹ Agegnehu Gettie,¹ Clarisa Buckner,¹ James Blanchard,² and Cecilia Cheng-Mayer^1*

Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York 10016,¹ Tulane National Primate Research Center, Tulane University Medical Center, Covington, Louisiana 70433²

Received 2 July 2002/ Accepted 27 September 2002

Through rapid serial transfer in vivo, the chimeric CCR5-tropic simian/human immunodeficiency virus SHIV_SF162 evolved from a virus that is nonpathogenic and poorly transmissible across the vaginal mucosa to a variant that still maintains CCR5 usage but which is now pathogenic and establishes intravaginal infection efficiently. To determine whether envelope glycoprotein gp120 is responsible for increased pathogenesis and transmissibility of the variant SHIV_SF162P3, we cloned and sequenced the dominant envelope gene (encoding P3 gp120) and characterized its functions in vitro. Chimeric SHIV_SF162 virus expressing P3 gp120 of the pathogenic variant, designated SHIV_SF162PC, was also constructed and assessed for its pathogenicity and mucosal transmissibility in vivo. We found that, compared to wild-type SHIV_SF162 gp120, P3 gp120 conferred in vitro neutralization resistance and increased entry efficiency of the virus but was compromised in its fusion-inducing capacity. In vivo, SHIV_SF162PC infected two of two and two of three rhesus macaques by the intravenous and intravaginal routes, respectively. Nevertheless, although peak viremia reached 10⁶ to 10⁷ RNA copies per ml of plasma in some infected animals and was associated with depletion of gut-associated CD4⁺ lymphocytes, none of the animals maintained a viral set point that would be predictive of progression to disease. Together, the data from this study suggest a lack of correlation between entry efficiency and cytopathic properties of envelope glycoproteins with viral pathogenicity. Furthermore, whereas env gp120 contains the determinant for enhanced mucosal transmissibility of SHIV_SF162P3, the determinant(s) of its increased virulence may require additional sequence changes in env gp41 and/or maps to other viral genes.

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* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Ave., 7th Floor, New York, NY 10016. Phone: (212) 448-5080. Fax: (212) 448-5158. E-mail: cmayer{at}adarc.org.

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Journal of Virology, January 2003, p. 989-998, Vol. 77, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.2.989-998.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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