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Journal of Virology, December 2005, p. 14887-14898, Vol. 79, No. 23
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.23.14887-14898.2005
CD8+ and CD20+ Lymphocytes Cooperate To Control Acute Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys: Modulation by Major Histocompatibility Complex Genotype
Hanwen Mao,
Bernard A. P. Lafont,
Tatsuhiko Igarashi,
Yoshiaki Nishimura,
Charlie Brown,
Vanessa Hirsch,
Alicia Buckler-White,
Reza Sadjadpour, and
Malcolm A. Martin*
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
Received 21 July 2005/
Accepted 5 September 2005
We have previously described two isogenic molecularly cloned simian immunodeficiency virus/human immunodeficiency virus chimeric viruses (SHIVs) that differ from one another by 9 amino acids and direct distinct clinical outcomes in inoculated rhesus monkeys. SHIVDH12R-Clone 7, like other highly pathogenic CXCR4-tropic SHIVs, induces rapid and complete depletions of CD4+ T lymphocytes and immunodeficiency in infected animals. In contrast, macaques inoculated with SHIVDH12R-Clone 8 experience only partial and transient losses of CD4+ T cells, show prompt control of their viremia, and remain healthy for periods of time extending for up to 4 years. The contributions of CD8+ and CD20+ lymphocytes in suppressing the replication of the attenuated SHIVDH12R-Clone 8 and maintaining a prolonged asymptomatic clinical course was assessed by treating animals with monoclonal antibodies that deplete each lymphocyte subset at the time of virus inoculation. The absence of either CD8+ or CD20+ cells during the SHIVDH12R-Clone 8 acute infection resulted in the rapid, complete, and irreversible loss of CD4+ T cells; sustained high levels of postpeak plasma viremia; and symptomatic disease in Mamu-A*01-negative Indian rhesus monkeys. In Mamu-A*01-positive animals, however, the aggressive, highly pathogenic phenotype was observed only in macaques depleted of CD8+ cells; SHIVDH12R-Clone 8 was effectively controlled in Mamu-A*01-positive monkeys in the absence of B lymphocytes. Taken together, these results indicate that both CD8+ and CD20+ B cells contribute to the control of primate lentiviral infection in Mamu-A*01-negative macaques. Furthermore, the major histocompatibility complex genotype of an infected animal, as exemplified by the Mamu-A*01 allele in this study, has the additional capacity to shift the balance of the composite immune response.
* Corresponding author. Mailing address: NIAID, NIH, Bldg. 4, Room 315, 4 Center Drive, MSC 0460, Bethesda, MD 20892-0460. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail:
malm{at}nih.gov.
Journal of Virology, December 2005, p. 14887-14898, Vol. 79, No. 23
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.23.14887-14898.2005
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