Importance of B-cell responses for immunological control of variant strains of simian immunodeficiency virus

Welkin E. Johnson, Jeffrey D. Lifson, Sabine M. Lang, R. Paul Johnson, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

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Abstract

The properties of three variants of cloned simian immunodeficiency virus strain 239 (SIV239) were compared. One strain (M5) lacked five sites for N-linked carbohydrate attachment in variable regions 1 and 2 (V1 and V2) of the gp120 envelope protein, one strain (ΔV1-V2) completely lacked V1 and V2 sequences, and another (316) had nine mutations in the envelope that impart high replicative capacity for tissue macrophages. All three strains were capable of significant levels of fusion independent of CD4, and all three were considerably more sensitive to antibody-mediated neutralization than the parent strain from which they were derived. Upon experimental infection of rhesus monkeys, these three variant strains replicated to viral loads at peak height around day 14 that were indistinguishable from or only slightly less than those observed in monkeys infected with the parental SIV239 strain. Viral loads at the set point 20 to 50 weeks after infection, however, were more than 400- to 10,000-fold lower with the variant strains. Depletion of B cells around the time of infection with M5 resulted in less effective immunological control and much higher viral loads at the set point in two of three monkeys. The differences between SIV239 infection, where there is not effective immunological control, and SIVM5 infection, where there is effective immunological control, cannot be easily explained by differences in the inherent replicative capacity of the viruses; rather, they are more readily explained by differences in the effectiveness of the antibody response. These results suggest that resistance of SIV239 to antibody-mediated neutralization is very important for evading effective immunological control, for allowing continuous viral replication, for maintenance of moderate-to-high viral loads at set point, and for disease progression.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalJournal of Virology
Volume77
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Viral Load
B-lymphocytes
B-Lymphocytes
immune response
Infection
Haplorhini
viral load
Antibodies
Infection Control
Macaca mulatta
Antibody Formation
Disease Progression
infection
Macrophages
Maintenance
Carbohydrates
neutralization
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Importance of B-cell responses for immunological control of variant strains of simian immunodeficiency virus. / Johnson, Welkin E.; Lifson, Jeffrey D.; Lang, Sabine M.; Paul Johnson, R.; Desrosiers, Ronald Charles.

In: Journal of Virology, Vol. 77, No. 1, 01.2003, p. 375-381.

Research output: Contribution to journalArticle

Johnson, Welkin E. ; Lifson, Jeffrey D. ; Lang, Sabine M. ; Paul Johnson, R. ; Desrosiers, Ronald Charles. / Importance of B-cell responses for immunological control of variant strains of simian immunodeficiency virus. In: Journal of Virology. 2003 ; Vol. 77, No. 1. pp. 375-381.
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