A Simian Immunodeficiency Virus-Infected Macaque Model To Study Viral Reservoirs That Persist during Highly Active Antiretroviral Therapy
| Autor: | Joel N. Blankson, Janice E. Clements, Robert F. Siliciano, Joseph L. Mankowski, S. Alireza Rabi, M. Christine Zink, Lucio Gama, Jason B. Dinoso |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology Simian Acquired Immunodeficiency Syndrome Spleen Viremia medicine.disease_cause Microbiology Macaque Virus Antiretroviral Therapy Highly Active Virology biology.animal Virus latency medicine Animals Lymphocyte Count biology virus diseases Simian immunodeficiency virus medicine.disease biology.organism_classification Virus Latency Disease Models Animal medicine.anatomical_structure Insect Science Lentivirus Macaca Pathogenesis and Immunity Simian Immunodeficiency Virus Lymph Nodes Lymph |
| Zdroj: | Journal of Virology. 83:9247-9257 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.00840-09 |
| Popis: | The treatment of human immunodeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART), a combination of three or more antiretroviral drugs, suppresses viremia below the clinical limit of detection (50 HIV-1 RNA copies/ml), but latently infected resting CD4 + T cells serve as lifelong reservoirs, and low-level viremia can be detected with special assays. Recent studies have provided evidence for additional reservoirs that contribute to residual viremia but are not present in circulating cells. Identification of all the sources of residual viremia in humans may be difficult. These discoveries highlight the need for a tractable model system to identify additional viral reservoirs that could represent barriers to eradication. In this study, simian immunodeficiency virus (SIV)-infected pig-tailed macaques ( Macaca nemestrina ) were treated with four antiretroviral drugs to develop an animal model for viral suppression during effective HAART. Treatment led to a biphasic decay in viremia and a significant rise in levels of circulating CD4 + T cells. At terminal infection time points, the frequency of circulating resting CD4 + T cells harboring replication-competent virus was reduced to a low steady-state level similar to that observed for HIV-infected patients on HAART. The frequencies of resting CD4 + T cells harboring replication-competent virus in the pooled head lymph nodes, gut lymph nodes, spleen, and peripheral blood were reduced relative to those for untreated SIV-infected animals. These observations closely parallel findings for HIV-infected humans on suppressive HAART and demonstrate the value of this animal model to identify and characterize viral reservoirs persisting in the setting of suppressive antiretroviral drugs. |
| Databáze: | OpenAIRE |
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