The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes.
Open accessAbstract
The viral regulatory gene, nef, is unique to the human immunodeficiency viruses (HIV) and their related primate lentiviruses. Expression of the nef gene has been shown to be essential to the maintenance of high levels of virus replication and the development of pathogenesis in the animal model of simian immunodeficiency virus (SIV) infection. In contrast to this in vivo model, the use of standard T cell culture systems to study nef function in vitro has produced a spectrum of contradictory results, and has failed to demonstrate a significant positive influence of nef on viral life cycle. We have developed a cell model to study regulation of HIV-1 replication that we believe reflects more accurately virus-cell interactions as they occur in vivo. Our experimental system used acute virus infection of purified, quiescent CD4 lymphocytes and subsequent induction of viral replication through T cell activation. With this cell model, NL4-3 virus clones with open and mutated nef reading frames were compared for replication competence. The clones with nef mutations showed reproducible and significant reductions in both rates of growth and maximal titers achieved. The degree of reduced replication was dependent on initial virus inoculum and the timing of T cell activation. The influence of nef was highly significant for induction of virus replication from a latent state within resting CD4 cells. Its effect was less apparent for virus infection of fully proliferating CD4 cells. This study demonstrates that nef confers a positive growth advantage to HIV-1 that becomes readily discernable in the primary cell setting of virus induction through T cell activation. The experimental cell model, which we describe here, provides not only a means to study nef function in vitro, but also provides important clues to the function of nef in HIV infection in vivo.
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Cites
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Cited by
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
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Pathogenicity of Live, Attenuated SIV After Mucosal Infection of Neonatal Macaques
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Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene
Chowers, M. Y., Spina, C. A., Kwoh, T. J., Fitch, N. J., Richman, D. D., & Guatelli, J. C. (1994) · Journal of Virology · doi:10.1128/jvi.68.5.2906-2914.1994 · Cited by 364
Self-citation
Metadata
- Authors
- Spina, C. A., Kwoh, T. J., Chowers, M. Y., Guatelli, J. C., & Richman, D. D.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-01-01
- Volume
- 179
- Issue
- 1
- Pages
- 115-123
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2130874555
- Cited by
- 391
- References
- 37
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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