NDLI: In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies.

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In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies.

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In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Berkhout, B. Verhoef, K. Marzio, G. Vink, M.
Description	Author Affiliation: Marzio G ( Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.);
Abstract	A major concern associated with the use of vaccines based on live-attenuated viruses is the possible and well documented reversion to pathogenic phenotypes. In the case of HIV, genomic deletions or mutations introduced to attenuate viral pathogenicity can be repaired by selection of compensating mutations. These events lead to increased virus replication rates and, eventually, disease progression. Because replication competence and degree of protection appear to be directly correlated, further attenuation of a vaccine virus may compromise the ability to elicit a protective immune response. Here, we describe an approach toward a safe attenuated HIV vaccine. The system is not based on permanent reduction of infectivity by alteration of important viral genomic sequences, but on strict control of replication through the insertion of the tetracycline (Tet) system in the HIV genome. Furthermore, extensive in vitro evolution was applied to the prototype Tet-controlled HIV to select for variants with optimized rather than diminished replication capacity. The final product of evolution has properties uniquely suited for use as a vaccine strain. The evolved virus is highly infectious, as opposed to a canonically attenuated virus. It replicates efficiently in T cell lines and in activated and unstimulated peripheral blood mononuclear cells. Most importantly, replication is strictly dependent on the nontoxic Tetanalogue doxycycline and can be turned on and off. These results suggest that this in vitro evolved, doxycycline-dependent HIV might represent a useful tool toward the development of a safer, live-attenuated HIV vaccine.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	AIDS Vaccines Anti-Bacterial Agents Pharmacology Doxycycline HIV-1 Physiology Virus Replication Drug Effects Genetics Cells, Cultured Directed Molecular Evolution Growth & Development Molecular Sequence Data T-Lymphocytes Cytology Time Factors Tumor Cells, Cultured Vaccines, Attenuated Virus Activation Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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