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Journal of Virology, January 2004, p. 275-284, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.275-284.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immune Failure in the Absence of Profound CD4+ T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques

Vanessa M. Hirsch,1* Sampa Santra,2 Simoy Goldstein,1 Ronald Plishka,1 Alicia Buckler-White,1 Aruna Seth,2 Ilnour Ourmanov,1 Charles R. Brown,1 Ronald Engle,3 David Montefiori,4 Jennifer Glowczwskie,5 Kevin Kunstman,5 Steven Wolinsky,5 and Norman L. Letvin2

Laboratory of Molecular Microbiology,1 Hepatitis Section, Laboratory of Infectious Diseases, National Institute of AllergyInfectious Disease, National Institutes of Health, Rockville, Maryland,3 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts,2 Department of Surgery, Duke University Medical Center, Durham, North Carolina,4 Division of Infectious Diseases, Department of Medicine, Northwestern University Medical School, Chicago, Illinois5

Received 16 July 2003/ Accepted 26 September 2003

A fraction of simian immunodeficiency virus (SIV)-infected macaques develop rapidly progressive disease in the apparent absence of detectable SIV-specific antibody responses. To characterize the immunopathogenesis of this syndrome, we studied viral load, CD4+ T-lymphocyte numbers as well as cellular and humoral immune responses to SIV and other exogenous antigens in four SIVsm-infected rhesus macaques that progressed to AIDS 9 to 16 weeks postinoculation. Each of these animals exhibited high levels of viremia but showed relatively preserved CD4 T lymphocytes in blood and lymphoid tissues at the time of death. Transient SIV-specific antibody responses and cytotoxic T-lymphocyte responses were observed at 2 to 4 weeks postinoculation. Two of the macaques that were immunized sequentially with tetanus toxoid and hepatitis A virus failed to develop antibody to either antigen. These studies show that the SIV-infected rapid progressor macaques initially mounted an appropriate but transient cellular and humoral immune response. The subsequent immune defect in these animals appeared to be global, affecting both cellular and humoral immunity to SIV as well as immune responses against unrelated antigens. The lack of CD4 depletion and loss of humoral and cellular immune responses suggest that their immune defect may be due to an early loss in T helper function.

* Corresponding author. Mailing address: Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Rockville, MD 20852. Phone: (301) 496-0559. Fax: (301) 496-0559. E-mail: vhirsch{at}nih.gov.

Journal of Virology, January 2004, p. 275-284, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.275-284.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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