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Journal of Virology, February 2002, p. 1731-1743, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1731-1743.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Administration of Recombinant Rhesus Interleukin-12 during Acute Simian Immunodeficiency Virus (SIV) Infection Leads to Decreased Viral Loads Associated with Prolonged Survival in SIVmac251-Infected Rhesus Macaques

A. A. Ansari,1* A. E. Mayne,1 J. B. Sundstrom,1 P. Bostik,1 B. Grimm,1 J. D. Altman,2 and F. Villinger1

Department of Pathology and Laboratory Medicine,1 Department of Microbiology, Emory University School of Medicine, Atlanta, Georgia 303222

Received 31 July 2001/ Accepted 14 November 2001

The ability of recombinant rhesus interleukin-12 (rMamu-IL-12) administration during acute simian immunodeficiency virus SIVmac251 infection to influence the quality of the antiviral immune responses was assessed in rhesus macaques. Group I (n = 4) was the virus-only control group. Group II and III received a conditioning regimen of rMamu-IL-12 (10 and 20 µg/kg, respectively, subcutaneously [s.c.]) on days -2 and 0. Thereafter, group II received 2 µg of IL-12 per kg and group III received 10 µg/kg s.c. twice a week for 8 weeks. On day 0 all animals were infected with SIVmac251 intravenously. While all four group I animals and three of four group II animals died by 8 and 10 months post infection (p.i.), all four group III animals remained alive for >20 months p.i. The higher IL-12 dose led to lower plasma viral loads and markedly lower peripheral blood mononuclear cell and lymph node proviral DNA loads. During the acute viremia phase, the high-IL-12-dose monkeys showed an increase in CD3- CD8{alpha}/{alpha}+ and CD3+ CD8 {alpha}/{alpha}+ cells and, unlike the control and low-IL-12-dose animals, did not demonstrate an increase in CD4+ CD45RA+ CD62L+ naive cells. The high-IL-12-dose animals also demonstrated that both CD8{alpha}/{alpha}+ and CD8{alpha}/ß+ cells produced antiviral factors early p.i., whereas only CD8{alpha}/ß+ cells retained this function late p.i. Long-term survival correlated with sustained high levels of SIV gag/pol and SIV env cytotoxic T lymphocytes and retention of high memory responses against nominal antigens. This is the first study to demonstrate the capacity of IL-12 to significantly protect macaques from SIV-induced disease, and it provides a useful model to more precisely identify correlates of virus-specific disease-protective responses.

* Corresponding author. Mailing address: Winship Cancer Institute, 1365B Clifton Rd., Rm 4107, Atlanta, GA 30322. Phone: (404) 778-5399. Fax: (404) 778-5016. E-mail: pathaaa{at}emory.edu.

Journal of Virology, February 2002, p. 1731-1743, Vol. 76, No. 4
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.4.1731-1743.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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