TY - JOUR
T1 - Development of virus-specific immune responses in SHIVKU-infected macaques treated with PMPA
AU - Kumar, Anil
AU - Buch, Shilpa
AU - Foresman, Larry
AU - Bischofberger, Norbert
AU - Lifson, Jeffrey D.
AU - Narayan, Opendra
N1 - Funding Information:
We thank F. Jia for excellent technical assistance. We also thank Drs. N. L. Letvin for Herpesvirus papio and D. Panicali and G. Mazzara for recombinant vaccinia viruses expressing HIV-1-Env, SIV-Gag, and SIV-Pol. The work was supported by National Institutes of Health, Grants AI-29382, RR-13152, RR-06753, and NS-32203 and, in part, with federal funds from the National Cancer Institute, National Institutes of Health under contract No. NO1-CO-56000.
PY - 2001/1/20
Y1 - 2001/1/20
N2 - Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to the suppression of HIV viremia below the threshold of detection for several years. However, impact of HAART on reconstitution of virus-specific immune responses remains poorly understood. In this study, four macaques were infected with pathogenic SHIVKU. One week postinoculation two of the four animals were treated with PMPA [9-R-(2-phosphophomethoxypropyl)adenine] daily for 83 days. Two other macaques, that did not receive treatment, exhibited explosive virus replication accompanied by a near total loss of CD4+ T cells and succumbed to AIDS-related complications within 6 months of infection. These animals did not develop any virus-specific immune responses. On the contrary, the animals that received PMPA showed transient loss of CD4+ T cells that recovered during the treatment period. The virus burden declined below the level of detection that rebounded soon after cessation of PMPA therapy. The virus replicated productively for several weeks before both animals controlled the productive replication of virus. This control of virus replication was found to be associated with the development of virus-specific neutralizing antibodies, T-helper cells, and CTLs. Although PMPA did not eliminate virus from the animals, it provided them with enough time to mount virus-specific immune responses that eventually controlled the virus replication in the blood. Our results suggest that antiretroviral therapy, if initiated early during infection, would help the host in mounting virus-specific immune responses that might control productive replication of the virus.
AB - Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to the suppression of HIV viremia below the threshold of detection for several years. However, impact of HAART on reconstitution of virus-specific immune responses remains poorly understood. In this study, four macaques were infected with pathogenic SHIVKU. One week postinoculation two of the four animals were treated with PMPA [9-R-(2-phosphophomethoxypropyl)adenine] daily for 83 days. Two other macaques, that did not receive treatment, exhibited explosive virus replication accompanied by a near total loss of CD4+ T cells and succumbed to AIDS-related complications within 6 months of infection. These animals did not develop any virus-specific immune responses. On the contrary, the animals that received PMPA showed transient loss of CD4+ T cells that recovered during the treatment period. The virus burden declined below the level of detection that rebounded soon after cessation of PMPA therapy. The virus replicated productively for several weeks before both animals controlled the productive replication of virus. This control of virus replication was found to be associated with the development of virus-specific neutralizing antibodies, T-helper cells, and CTLs. Although PMPA did not eliminate virus from the animals, it provided them with enough time to mount virus-specific immune responses that eventually controlled the virus replication in the blood. Our results suggest that antiretroviral therapy, if initiated early during infection, would help the host in mounting virus-specific immune responses that might control productive replication of the virus.
KW - AIDS
KW - Antibodies
KW - Antiretroviral treatment
KW - CTL
KW - In vivo animal models
KW - SHIV
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U2 - 10.1006/viro.2000.0710
DO - 10.1006/viro.2000.0710
M3 - Article
C2 - 11145893
AN - SCOPUS:0035915990
SN - 0042-6822
VL - 279
SP - 97
EP - 108
JO - Virology
JF - Virology
IS - 1
ER -