Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion.
DC-SIGN
HIV-1
Vpu
antibodies
envelope
glycosylation
tetherin antagonism
transmission
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
13 04 2022
13 04 2022
Historique:
received:
01
02
2022
revised:
08
04
2022
accepted:
11
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
HIV-1 Env signal peptide (SP) is an important contributor to Env functions. Env is generated from Vpu/Env encoded bicistronic mRNA such that the 5' end of Env-N-terminus, that encodes for Env-SP overlaps with 3' end of Vpu. Env SP displays high sequence diversity, which translates into high variability in Vpu sequence. This study aimed to understand the effect of sequence polymorphism in the Vpu-Env overlapping region (VEOR) on the functions of two vital viral proteins: Vpu and Env. We used infectious molecular clone pNL4.3-CMU06 and swapped its SP (or VEOR) with that from other HIV-1 isolates. Swapping VEOR did not affect virus production in the absence of tetherin however, presence of tetherin significantly altered the release of virus progeny. VEOR also altered Vpu's ability to downregulate CD4 and tetherin. We next tested the effect of these swaps on Env functions. Analyzing the binding of monoclonal antibodies to membrane embedded Env revealed changes in the antigenic landscape of swapped Envs. These swaps affected the oligosaccharide composition of Env-N-glycans as shown by changes in DC-SIGN-mediated virus transmission. Our study suggests that genetic diversity in VEOR plays an important role in the differential pathogenesis and also assist in immune evasion by altering Env epitope exposure.
Identifiants
pubmed: 35458538
pii: v14040808
doi: 10.3390/v14040808
pmc: PMC9030904
pii:
doi:
Substances chimiques
Bone Marrow Stromal Antigen 2
0
GPI-Linked Proteins
0
Human Immunodeficiency Virus Proteins
0
Protein Sorting Signals
0
Viral Regulatory and Accessory Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI140909
Pays : United States
Organisme : NIAID NIH HHS
ID : AI140909
Pays : United States
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