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Human Immunodeficiency Virus Type 1 mRNA Expression in Peripheral Blood Cells Predicts Disease Progression Independently of the Numbers of CD4+ Lymphocytes

Saksela, Kalle and Stevens, Cladd and Rubinstein, Pablo and Baltimore, David (1994) Human Immunodeficiency Virus Type 1 mRNA Expression in Peripheral Blood Cells Predicts Disease Progression Independently of the Numbers of CD4+ Lymphocytes. Proceedings of the National Academy of Sciences of the United States of America, 91 (3). pp. 1104-1108. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:SAKpnas94

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Abstract

To address the significance of human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells (PBMCs), we have used reverse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals during a long-term prospective study. We found dramatic differences in HIV mRNA expression among individuals with very similar clinical and laboratory indices, and this variation strongly correlated with the future course of the disease. No evidence of viral replication was detected in PBMCs from asymptomatic individuals who, thereafter, had normal levels of CD4+ cells for at least 5 years. Irrespective of whether the CD4+ cell numbers were normal at the time of sampling, abundant expression of HIV-1 mRNA in PBMCs predicted accelerated disease progression within the next 2 years. Thus, independently of what may be the rate of HIV replication in other viral reservoirs, such as lymphatic tissue, the amount of HIV mRNA in PBMCs appears to reflect the subsequent development of HIV disease. We have also used the reverse transcriptase-initiated PCR assay to demonstrate a transient response to 3'-azido-3'-deoxythymidine treatment. Determination of HIV-1 mRNA expression in the PBMCs of infected individuals could, therefore, have significant clinical utility as a prognostic indicator and as a means to guiding and monitoring antiviral therapies.


Item Type:Article
Additional Information:Copyright © 1994 by National Academy of Sciences. Contributed by David Baltimore, October 18, 1993. We thank Dr. Roger Pomerantz for discussions and the plasmids used for in vitro transcription of HIV RNAs and Dr. David Ho and other investigators at the Aaron Diamond AIDS Research Center for discussions and the opportunity to use their facilities. K.S. is an Aaron Diamond Foundation postdoctoral research fellow. This study was supported by National Institutes of Health Grant A122346 to D.B. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:acquired immunodeficiency syndrome; polymerase chain reaction; 3'-azido-3'-deoxythymidine
Record Number:CaltechAUTHORS:SAKpnas94
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:SAKpnas94
Alternative URL:http://www.pnas.org/cgi/content/abstract/91/3/1104
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9560
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:04 Feb 2008
Last Modified:14 Nov 2014 19:20

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