PMID- 34529947
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20230503
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 120
IP  - 21
DP  - 2021 Nov 2
TI  - Stability and conformation of the dimeric HIV-1 genomic RNA 5'UTR.
PG  - 4874-4890
LID - S0006-3495(21)00751-7 [pii]
LID - 10.1016/j.bpj.2021.09.017 [doi]
AB  - During HIV-1 assembly, the viral Gag polyprotein specifically selects the dimeric 
      RNA genome for packaging into new virions. The 5' untranslated region (5'UTR) of 
      the dimeric genome may adopt a conformation that is optimal for recognition by 
      Gag. Further conformational rearrangement of the 5'UTR, promoted by the 
      nucleocapsid (NC) domain of Gag, is predicted during virus maturation. Two 5'UTR 
      dimer conformations, the kissing dimer (KD) and the extended dimer (ED), have 
      been identified in vitro, which differ in the extent of intermolecular 
      basepairing. Whether 5'UTRs from different HIV-1 strains with distinct sequences 
      have access to the same dimer conformations has not been determined. Here, we 
      applied fluorescence cross-correlation spectroscopy and single-molecule Forster 
      resonance energy transfer imaging to demonstrate that 5'UTRs from two different 
      HIV-1 subtypes form (KDs) with divergent stabilities. We further show that both 
      5'UTRs convert to a stable dimer in the presence of the viral NC protein, 
      adopting a conformation consistent with extensive intermolecular contacts. These 
      results support a unified model in which the genomes of diverse HIV-1 strains 
      adopt an ED conformation.
CI  - Copyright (c) 2021 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Blakemore, Robert J
AU  - Blakemore RJ
AD  - Department of Molecular Biology and Microbiology, Tufts University School of 
      Medicine and School of Graduate Biomedical Sciences, Boston, Massachusetts; 
      Graduate Program in Molecular Microbiology, Tufts University Graduate School of 
      Biomedical Sciences, Boston, Massachusetts.
FAU - Burnett, Cleo
AU  - Burnett C
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, Michigan.
FAU - Swanson, Canessa
AU  - Swanson C
AD  - Department of Chemistry and Biochemistry, University of Maryland Baltimore 
      Country, Baltimore, Maryland.
FAU - Kharytonchyk, Siarhei
AU  - Kharytonchyk S
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, Michigan.
FAU - Telesnitsky, Alice
AU  - Telesnitsky A
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, Michigan.
FAU - Munro, James B
AU  - Munro JB
AD  - Department of Molecular Biology and Microbiology, Tufts University School of 
      Medicine and School of Graduate Biomedical Sciences, Boston, Massachusetts; 
      Department of Microbiology and Physiological Systems, University of Massachusetts 
      Medical School, Worcester, Massachusetts; Department of Biochemistry and 
      Molecular Pharmacology, University of Massachusetts Medical School, Worcester, 
      Massachusetts. Electronic address: james.munro@umassmed.edu.
LA  - eng
GR  - R21 AI136711/AI/NIAID NIH HHS/United States
GR  - T32 AI007422/AI/NIAID NIH HHS/United States
GR  - U54 AI150470/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210914
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Genomics
MH  - *HIV-1/genetics
MH  - Nucleic Acid Conformation
MH  - Nucleocapsid
MH  - RNA, Viral/genetics
MH  - Virion
PMC - PMC8595565
EDAT- 2021/09/17 06:00
MHDA- 2021/11/16 06:00
PMCR- 2022/11/02
CRDT- 2021/09/16 20:11
PHST- 2021/06/07 00:00 [received]
PHST- 2021/08/13 00:00 [revised]
PHST- 2021/09/08 00:00 [accepted]
PHST- 2021/09/17 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2021/09/16 20:11 [entrez]
PHST- 2022/11/02 00:00 [pmc-release]
AID - S0006-3495(21)00751-7 [pii]
AID - 10.1016/j.bpj.2021.09.017 [doi]
PST - ppublish
SO  - Biophys J. 2021 Nov 2;120(21):4874-4890. doi: 10.1016/j.bpj.2021.09.017. Epub 
      2021 Sep 14.