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

doi:10.1128/JVI.01975-15

Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells

J Virol. 2015 Dec 4;90(4):2119-26. doi: 10.1128/JVI.01975-15. Print 2016 Feb 15.

Authors

Affiliations

¹ Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
² Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
³ Biomedical Sciences Training Program, Tulane University, New Orleans, Louisiana, USA.
⁴ Wisconsin National Primate Research Center, Madison, Wisconsin, USA Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
⁵ Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Sciences University, Portland, Oregon, USA.
⁶ Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA Department of Microbiology and Immunology, School of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
⁷ Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Sciences University, Portland, Oregon, USA Vaccine & Gene Therapy Institute, Oregon National Primate Research Center, Oregon Health and Sciences University, Portland, Oregon, USA.
⁸ Wisconsin National Primate Research Center, Madison, Wisconsin, USA Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin, USA.
⁹ Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA Department of Microbiology and Immunology, School of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA [email protected].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology*
Epitopes, T-Lymphocyte / genetics*
Epitopes, T-Lymphocyte / immunology*
High-Throughput Nucleotide Sequencing
Histocompatibility Antigens Class I / metabolism*
Macaca
Mutation, Missense*
Viral Regulatory and Accessory Proteins / genetics*
Viral Regulatory and Accessory Proteins / immunology
Viral Regulatory and Accessory Proteins / metabolism*

Substances

Epitopes, T-Lymphocyte
Histocompatibility Antigens Class I
NEF protein, SIV
Viral Regulatory and Accessory Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding