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Mouse Papillomavirus L1 and L2 Are Dispensable for Viral Infection and Persistence at Both Cutaneous and Mucosal Tissues.

Authors
  • Brendle, Sarah1, 2
  • Li, Jingwei J1, 2
  • Cladel, Nancy M1, 2
  • Shearer, Debra A1, 2
  • Budgeon, Lynn R1, 2
  • Balogh, Karla K1, 2
  • Atkins, Hannah3
  • Costa-Fujishima, Marina4
  • Lopez, Paul4
  • Christensen, Neil D1, 2, 5
  • Doorbar, John6
  • Murooka, Thomas T4
  • Hu, Jiafen1, 2
  • 1 The Jake Gittlen Laboratories for Cancer Research, Hershey, PA 17033, USA.
  • 2 Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • 3 Laboratory Medicine, Department of Pathology, Division of Comparative Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • 4 Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. , (Canada)
  • 5 Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • 6 Department of Pathology, Division of Virology, University of Cambridge, Tennis Court Road, Cambridge CB21 QP, UK.
Type
Published Article
Journal
Viruses
Publisher
MDPI AG
Publication Date
Sep 14, 2021
Volume
13
Issue
9
Identifiers
DOI: 10.3390/v13091824
PMID: 34578405
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Papillomavirus L1 and L2, the major and minor capsid proteins, play significant roles in viral assembly, entry, and propagation. In the current study, we investigate the impact of L1 and L2 on viral life cycle and tumor growth with a newly established mouse papillomavirus (MmuPV1) infection model. MmuPV1 L1 knockout, L2 knockout, and L1 plus L2 knockout mutant genomes (designated as L1ATGko-4m, L2ATGko, and L1-L2ATGko respectively) were generated. The mutants were examined for their ability to generate lesions in athymic nude mice. Viral activities were examined by qPCR, immunohistochemistry (IHC), in situ hybridization (ISH), and transmission electron microscopy (TEM) analyses. We demonstrated that viral DNA replication and tumor growth occurred at both cutaneous and mucosal sites infected with each of the mutants. Infections involving L1ATGko-4m, L2ATGko, and L1-L2ATGko mutant genomes generally resulted in smaller tumor sizes compared to infection with the wild type. The L1 protein was absent in L1ATGko-4m and L1-L2ATGko mutant-treated tissues, even though viral transcripts and E4 protein expression were robust. Therefore, L1 is not essential for MmuPV1-induced tumor growth, and this finding parallels our previous observations in the rabbit papillomavirus model. Very few viral particles were detected in L2ATGko mutant-infected tissues. Interestingly, the localization of L1 in lesions induced by L2ATGko was primarily cytoplasmic rather than nuclear. The findings support the hypothesis that the L2 gene influences the expression, location, transport, and assembly of the L1 protein in vivo.

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