|
Basic Characteristics of Mutations
|
|
Mutation Site
|
12_39del |
|
Mutation Site Sentence
|
Consistently, NEF Delta12-39 was also almost entirely defective in preventing actin polymerization in BHEL cells upon IS engagement (Fig 3C and D). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Deletion |
|
Gene/Protein/Region
|
Nef |
|
Standardized Encoding Gene
|
Nef
|
|
Genotype/Subtype
|
HIV-1 |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
Y |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
Nef |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
33146906
|
|
Title
|
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function
|
|
Author
|
Kaw S,Ananth S,Tsopoulidis N,Morath K,Coban BM,Hohenberger R,Bulut OC,Klein F,Stolp B,Fackler OT
|
|
Journal
|
The EMBO journal
|
|
Journal Info
|
2020 Dec 15;39(24):e105594
|
|
Abstract
|
Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B-cell dysfunction due to unspecific B-cell activation. How HIV-1 affects antigen-specific B-cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B-cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T-cell-B-cell immune synapse. This interference reduced B-cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
|
|
Sequence Data
|
-
|