PMID- 36160049
OWN - NLM
STAT- MEDLINE
DCOM- 20231012
LR  - 20240517
IS  - 2667-2375 (Electronic)
IS  - 2667-2375 (Linking)
VI  - 2
IP  - 9
DP  - 2022 Sep 19
TI  - A chemical method for generating live-attenuated, replication-defective DNA 
      viruses for vaccine development.
PG  - 100287
LID - 10.1016/j.crmeth.2022.100287 [doi]
LID - 100287
AB  - The development of a chemically attenuated, replication-incompetent virus vaccine 
      can provide protection against diseases caused by DNA viruses. In this study, we 
      have developed a method to produce live-attenuated, replication-defective viruses 
      using centanamycin (CM), a chemical compound that alkylates the A-T-rich minor 
      groove of the DNA and thereby blocks DNA replication. We tested the efficacy of 
      CM to produce live-attenuated, replication-defective human cytomegalovirus, mouse 
      cytomegalovirus, and herpes simplex virus-2 (HSV-2), suggesting a broad 
      application for generating live-attenuated, replication-defective DNA viruses. 
      Mass spectrometry analysis showed that CM alkylate viral DNA at the adenine-N3 
      position. Moreover, mice immunization with CM-attenuated mouse cytomegalovirus 
      (MCMV) produced a robust immune response and reduced the viral load in immunized 
      animals against challenges with live, wild-type MCMV. Our study offers a unifying 
      and attractive therapeutic opportunity that chemically attenuated live DNA 
      viruses can be readily developed as new frontline vaccines.
FAU - Jaijyan, Dabbu Kumar
AU  - Jaijyan DK
AD  - Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers - New 
      Jersey Medical School, 225 Warren Street, Newark, NJ 07103, USA.
FAU - Govindasamy, Kavitha
AU  - Govindasamy K
AD  - New Jersey Center for Science, Technology and Mathematics, Kean University, 
      Union, NJ, USA.
FAU - Lee, Moses
AU  - Lee M
AD  - Department of Chemistry, Georgia State University, Atlanta, GA, USA.
FAU - Zhu, Hua
AU  - Zhu H
AD  - Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers - New 
      Jersey Medical School, 225 Warren Street, Newark, NJ 07103, USA.
LA  - eng
GR  - U01 HL150852/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220908
PL  - United States
TA  - Cell Rep Methods
JT  - Cell reports methods
JID - 9918227360606676
RN  - 9007-49-2 (DNA)
MH  - Animals
MH  - Mice
MH  - Humans
MH  - *Herpesvirus 2, Human/genetics
MH  - *Immunization
MH  - Vaccination
MH  - DNA
MH  - Vaccine Development
PMC - PMC9499982
OTO - NOTNLM
OT  - CM
OT  - DNA viruses
OT  - centanamycin
OT  - cytomegalovirus
OT  - herpes simplex virus
OT  - inactivated viruses
OT  - live-attenuated viruses
OT  - vaccines
COIS- United States and worldwide patents have been filed based on the research 
      findings in this paper.
EDAT- 2022/09/27 06:00
MHDA- 2022/09/27 06:01
PMCR- 2022/09/08
CRDT- 2022/09/26 17:44
PHST- 2022/01/26 00:00 [received]
PHST- 2022/06/22 00:00 [revised]
PHST- 2022/08/17 00:00 [accepted]
PHST- 2022/09/26 17:44 [entrez]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/09/27 06:01 [medline]
PHST- 2022/09/08 00:00 [pmc-release]
AID - S2667-2375(22)00169-2 [pii]
AID - 100287 [pii]
AID - 10.1016/j.crmeth.2022.100287 [doi]
PST - epublish
SO  - Cell Rep Methods. 2022 Sep 8;2(9):100287. doi: 10.1016/j.crmeth.2022.100287. 
      eCollection 2022 Sep 19.