Acute viral escape selectively impairs nef-mediated major histocompatibility complex class i downmodulation and increases susceptibility to antiviral t cells

Andrea M. Weiler, Arpita Das, Oluwasayo Akinyosoye, Sherry Cui, Shelby L. O'Connor, Elizabeth A. Scheef, Jason S. Reed, Antonito T. Panganiban, Jonah B. Sacha, Eva G. Rakasz, Thomas C. Friedrich, Nicholas J. Maness

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Nef-specific CD8+ T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef-s major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication.

Original languageEnglish (US)
Pages (from-to)2119-2126
Number of pages8
JournalJournal of virology
Volume90
Issue number4
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Weiler, A. M., Das, A., Akinyosoye, O., Cui, S., O'Connor, S. L., Scheef, E. A., Reed, J. S., Panganiban, A. T., Sacha, J. B., Rakasz, E. G., Friedrich, T. C., & Maness, N. J. (2016). Acute viral escape selectively impairs nef-mediated major histocompatibility complex class i downmodulation and increases susceptibility to antiviral t cells. Journal of virology, 90(4), 2119-2126. https://doi.org/10.1128/JVI.01975-15