title: Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.
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.
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Weiler
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Arpita
authors.initials: A
authors.lastname: Das
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Oluwasayo
authors.initials: O
authors.lastname: Akinyosoye
authors.affiliation: Biomedical Sciences Training Program, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Cui
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: O'Connor
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Scheef
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Sciences University, Portland, Oregon, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Reed
authors.affiliation: 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.
authors.forename: Antonito T
authors.initials: AT
authors.lastname: Panganiban
authors.affiliation: 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.
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.affiliation: Wisconsin National Primate Research Center, Madison, Wisconsin, USA Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.affiliation: 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 nmaness@tulane.edu.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Maness
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008251:Macaca; D020125:Mutation, Missense; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins