PMID- 19389243
OWN - NLM
STAT- MEDLINE
DCOM- 20090601
LR  - 20231103
IS  - 1471-2180 (Electronic)
IS  - 1471-2180 (Linking)
VI  - 9
DP  - 2009 Apr 23
TI  - Cervical cancer isolate PT3, super-permissive for adeno-associated virus 
      replication, over-expresses DNA polymerase delta, PCNA, RFC and RPA.
PG  - 79
LID - 10.1186/1471-2180-9-79 [doi]
AB  - BACKGROUND: Adeno-associated virus (AAV) type 2 is an important virus due to its 
      use as a safe and effective human gene therapy vector and its negative 
      association with certain malignancies. AAV, a dependo-parvovirus, autonomously 
      replicates in stratified squamous epithelium. Such tissue occurs in the 
      nasopharynx and anogenitals, from which AAV has been clinically isolated. Related 
      autonomous parvoviruses also demonstrate cell tropism and preferentially 
      replicate in oncogenically transformed cells. Combining these two attributes of 
      parvovirus tropism, squamous and malignant, we assayed if AAV might replicate in 
      squamous cervical carcinoma cell isolates. RESULTS: Three primary isolates 
      (PT1-3) and two established cervical cancer cell lines were compared to normal 
      keratinocytes (NK) for their ability to replicate AAV. One isolate, PT3, allowed 
      for high levels of AAV DNA replication and virion production compared to others. 
      In research by others, four cellular components are known required for in vitro 
      AAV DNA replication: replication protein A (RPA), replication factor C (RFC), 
      proliferating cell nuclear antigen (PCNA), and DNA polymerase delta (POLD1). 
      Thus, we examined PT3 cells for expression of these components by DNA microarray 
      and real-time quantitative PCR. All four components were over-expressed in PT3 
      over two representative low-permissive cell isolates (NK and PT1). However, this 
      super-permissiveness did not result in PT3 cell death by AAV infection. 
      CONCLUSION: These data, for the first time, provide evidence that these four 
      cellular components are likely important for AAV in vivo DNA replication as well 
      as in vitro. These data also suggest that PT3 will be a useful reagent for 
      investigating the AAV-permissive transcriptome and AAV anti-cancer effect.
FAU - Kang, Bum Yong
AU  - Kang BY
AD  - Department of Internal Medicine, Gene Therapy Program, University of Arkansas for 
      Medical Sciences, 4301 West Markham St, Little Rock, AR 72205, USA. 
      BKang@uams.edu
FAU - You, Hong
AU  - You H
FAU - Bandyopadhyay, Sarmistha
AU  - Bandyopadhyay S
FAU - Agrawal, Nalini
AU  - Agrawal N
FAU - Melchert, Russell B
AU  - Melchert RB
FAU - Basnakian, Alexei G
AU  - Basnakian AG
FAU - Liu, Yong
AU  - Liu Y
FAU - Hermonat, Paul L
AU  - Hermonat PL
LA  - eng
GR  - CA104873/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090423
PL  - England
TA  - BMC Microbiol
JT  - BMC microbiology
JID - 100966981
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (Replication Protein A)
RN  - EC 2.7.7.7 (DNA Polymerase III)
RN  - EC 3.6.4.- (Replication Protein C)
SB  - IM
MH  - Cell Line, Tumor
MH  - DNA Polymerase III/genetics/*metabolism
MH  - DNA Replication
MH  - Dependovirus/genetics/*physiology
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Keratinocytes/metabolism/virology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Parvoviridae Infections/genetics
MH  - Proliferating Cell Nuclear Antigen/genetics/*metabolism
MH  - RNA, Neoplasm/metabolism
MH  - Replication Protein A/genetics/*metabolism
MH  - Replication Protein C/genetics/*metabolism
MH  - Uterine Cervical Neoplasms/genetics/*virology
MH  - Virus Replication
PMC - PMC2685399
EDAT- 2009/04/25 09:00
MHDA- 2009/06/02 09:00
PMCR- 2009/04/23
CRDT- 2009/04/25 09:00
PHST- 2008/08/15 00:00 [received]
PHST- 2009/04/23 00:00 [accepted]
PHST- 2009/04/25 09:00 [entrez]
PHST- 2009/04/25 09:00 [pubmed]
PHST- 2009/06/02 09:00 [medline]
PHST- 2009/04/23 00:00 [pmc-release]
AID - 1471-2180-9-79 [pii]
AID - 10.1186/1471-2180-9-79 [doi]
PST - epublish
SO  - BMC Microbiol. 2009 Apr 23;9:79. doi: 10.1186/1471-2180-9-79.