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A Novel HIV-1 Nef Mutation in a Primary Pediatric Isolate Impairs MHC-Class I Downregulation and Cytopathicity.
- Source :
-
AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2020 Feb; Vol. 36 (2), pp. 122-130. Date of Electronic Publication: 2019 Nov 04. - Publication Year :
- 2020
-
Abstract
- HIV-1-induced cytopathicity of thymocytes is a major cause of reduced peripheral T cells and rapid disease progression observed in HIV-1-infected infants. Understanding the virulence factors responsible for thymocyte depletion has paramount importance in addressing the pathogenesis of disease progression in children. In this study, thymocyte depletion was analyzed following infection with two primary CXCR4-tropic HIV-1 pediatric isolates (PI), PI-2 and PI-2.1, which were serially derived from an in utero -infected infant. Although highly similar to each other, PI-2 showed markedly decreased thymocyte depletion in vitro compared with PI-2.1. Further analysis showed a novel deletion in the Nef protein (NefΔK7S) of PI-2, which was absent in PI-2.1. This deletion inhibited Nef-mediated major histocompatibility complex class I (MHC-I) downregulation in infected thymocytes in vitro and in vivo ; in contrast, the mutated Nef continued to downregulate CD4 surface expression in vitro. These results suggest that HIV-1 Nef contributes to thymic damage in infants through selective functions.
- Subjects :
- Animals
Cells, Cultured
Child, Preschool
Cytopathogenic Effect, Viral
Down-Regulation
Gene Deletion
HIV Infections virology
HIV-1 genetics
Humans
Infant, Newborn
Mice
Mice, SCID
Mutation
Thymocytes pathology
HIV Infections genetics
Histocompatibility Antigens Class I genetics
Thymocytes virology
nef Gene Products, Human Immunodeficiency Virus genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1931-8405
- Volume :
- 36
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- AIDS research and human retroviruses
- Publication Type :
- Academic Journal
- Accession number :
- 31571497
- Full Text :
- https://doi.org/10.1089/AID.2019.0160