Identification of highly attenuated mutants of simian immunodeficiency virus

Ronald Charles Desrosiers, Jeffrey D. Lifson, James S. Gibbs, Susan C. Czajak, Anita Y M Howe, Larry O. Arthur, R. Paul Johnson

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

Deletion mutants of the pathogenic clone of simian immunodeficiency virus isolate 239 (SIVmac239) were derived that are missing nef, vpr, and upstream sequences (US) in the U3 region of the LTR (SIVmac239Δ3), nef, vpx, and US (SIVmac239Δ3x), and nef, vpr, vpx, and US (SIVmac239Δ4). These multiply deleted derivatives replicated well in the continuously growing CEMx174 cell line and were infectious for rhesus monkeys. However, on the basis of virus load measurements, strength of antibody responses, and lack of disease progression, these mutants were highly attenuated. Measurements of cell-associated viral load agreed well with assays of plasma viral RNA load and with the strengths of the antibody responses; thus, these measurements likely reflected the extent of vital replication in vivo. A derivative of SIVmac239 lacking vif sequences (SIVmac239Δvif) could be consistently grown only in a vif-complementing cell line. This Δvif virus appeared to be very weakly infectious for rhesus monkeys on the basis of sensitive antibody tests only. The weak antibody responses elicited by SIVmac239Δvif were apparently in response to low levels of replicating virus since they were not elicited by heat-inactivated virus and the anti-SIV antibody responses persisted for greater than 1 year. These results, and the results of previous studies, allow a rank ordering of the relative virulence of nine mutant strains of SIVmac according to the following order: Δvpr > Δvpx > ΔvprΔvpx ≃ Δnef > Δ3 > Δ3x ≤ Δ4 > Δvif > Δ5. The results also demonstrate that almost any desired level of attenuation can be achieved, ranging from still pathogenic in a significant proportion of animals (Δvpr and Δvpx) to not detectably infectious (Δ5), simply by varying the number and location of deletions in these five loci.

Original languageEnglish (US)
Pages (from-to)1431-1437
Number of pages7
JournalJournal of Virology
Volume72
Issue number2
StatePublished - Feb 1998
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Antibody Formation
Viruses
mutants
antibodies
Macaca mulatta
Viral Load
viral load
viruses
Cell Line
chemical derivatives
cell lines
Viral RNA
Virulence
Disease Progression
Anti-Idiotypic Antibodies
disease course
Clone Cells
Hot Temperature

ASJC Scopus subject areas

  • Immunology

Cite this

Desrosiers, R. C., Lifson, J. D., Gibbs, J. S., Czajak, S. C., Howe, A. Y. M., Arthur, L. O., & Johnson, R. P. (1998). Identification of highly attenuated mutants of simian immunodeficiency virus. Journal of Virology, 72(2), 1431-1437.

Identification of highly attenuated mutants of simian immunodeficiency virus. / Desrosiers, Ronald Charles; Lifson, Jeffrey D.; Gibbs, James S.; Czajak, Susan C.; Howe, Anita Y M; Arthur, Larry O.; Johnson, R. Paul.

In: Journal of Virology, Vol. 72, No. 2, 02.1998, p. 1431-1437.

Research output: Contribution to journalArticle

Desrosiers, RC, Lifson, JD, Gibbs, JS, Czajak, SC, Howe, AYM, Arthur, LO & Johnson, RP 1998, 'Identification of highly attenuated mutants of simian immunodeficiency virus', Journal of Virology, vol. 72, no. 2, pp. 1431-1437.
Desrosiers RC, Lifson JD, Gibbs JS, Czajak SC, Howe AYM, Arthur LO et al. Identification of highly attenuated mutants of simian immunodeficiency virus. Journal of Virology. 1998 Feb;72(2):1431-1437.
Desrosiers, Ronald Charles ; Lifson, Jeffrey D. ; Gibbs, James S. ; Czajak, Susan C. ; Howe, Anita Y M ; Arthur, Larry O. ; Johnson, R. Paul. / Identification of highly attenuated mutants of simian immunodeficiency virus. In: Journal of Virology. 1998 ; Vol. 72, No. 2. pp. 1431-1437.
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