PMID- 35862992
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20221012
IS  - 2165-0497 (Electronic)
IS  - 2165-0497 (Linking)
VI  - 10
IP  - 4
DP  - 2022 Aug 31
TI  - Persistent Reptarenavirus and Hartmanivirus Infection in Cultured Boid Cells.
PG  - e0158522
LID - 10.1128/spectrum.01585-22 [doi]
LID - e01585-22
AB  - Mammarenaviruses establish a persistent infection in their rodent and bat hosts, 
      and the evidence suggests that reptarenaviruses and hartmaniviruses found in 
      captive snakes act similarly. In snakes, reptarenaviruses cause boid inclusion 
      body disease (BIBD), which is often associated with secondary infections. Snakes 
      with BIBD usually carry more than a single pair of reptarenavirus S and L 
      segments and occasionally demonstrate hartmanivirus coinfection. Here, we 
      reported the generation of cell lines persistently infected with a single or two 
      reptarenavirus(es) and a cell line with persistent reptarenavirus-hartmanivirus 
      coinfection. By RT-PCR we demonstrated that the amount of viral RNA within the 
      persistently infected cells remains at levels similar to those observed following 
      initial infection. Using antibodies against the glycoproteins (GPs) and 
      nucleoprotein (NP) of reptarenaviruses, we studied the levels of viral protein in 
      cells passaged 10 times after the original inoculation and observed that the 
      expression of GPs declines dramatically during persistent infection, unlike the 
      expression of NP. Immunofluorescence (IF) staining served to demonstrate 
      differences in the distribution of NP within the persistently infected compared 
      to freshly infected cells. IF staining of cells inoculated with the viruses 
      secreted from the persistently infected cell lines produced similar NP staining 
      compared to cells infected with a traditionally passaged virus, suggesting that 
      the altered NP expression pattern of persistently infected cells does not relate 
      to changes in the virus. The cell cultures described herein can serve as tools 
      for studying the coinfection and superinfection interplay between 
      reptarenaviruses and studying the BIBD pathogenesis mechanisms. IMPORTANCE 
      Mammarenaviruses cause a persistent infection in their natural rodent and bat 
      hosts. Reptarenaviruses cause boid inclusion body disease (BIBD) in constrictor 
      snakes, but it is unclear whether snakes are the natural host of these viruses. 
      In this study, we showed that reptarenaviruses established a persistent infection 
      in cultured Boa constrictor cells and that the persistently infected cells 
      continued to produce infectious virus. Our results showed that persistent 
      infection results from subsequent passaging of cells inoculated with a single 
      reptarenavirus, two reptarenaviruses, or even when inoculating the cells with 
      reptarenavirus and hartmanivirus (another arenavirus genus). The results further 
      suggested that coinfection would not result in overt competition between the 
      different reptarenaviruses, thus helping to explain the frequent reptarenavirus 
      coinfections in snakes with BIBD. The established cell culture models of 
      persistent infection could help to elucidate the role of coinfection and 
      superinfection and potential immunosuppression as the pathogenic mechanisms 
      behind BIBD.
FAU - Lintala, Annika
AU  - Lintala A
AD  - University of Helsinki, Faculty of Medicine, Medicum, Department of Virology, 
      Helsinki, Finland.
FAU - Szirovicza, Leonora
AU  - Szirovicza L
AUID- ORCID: 0000-0003-1528-044X
AD  - University of Helsinki, Faculty of Medicine, Medicum, Department of Virology, 
      Helsinki, Finland.
FAU - Kipar, Anja
AU  - Kipar A
AUID- ORCID: 0000-0001-7289-3459
AD  - University of Zurich, Vetsuisse Faculty, Institute of Veterinary Pathology, 
      Zurich, Switzerland.
AD  - University of Helsinki, Faculty of Veterinary Medicine, Department of Basic 
      Veterinary Sciences, Helsinki, Finland.
FAU - Hetzel, Udo
AU  - Hetzel U
AD  - University of Zurich, Vetsuisse Faculty, Institute of Veterinary Pathology, 
      Zurich, Switzerland.
AD  - University of Helsinki, Faculty of Veterinary Medicine, Department of Basic 
      Veterinary Sciences, Helsinki, Finland.
FAU - Hepojoki, Jussi
AU  - Hepojoki J
AUID- ORCID: 0000-0001-5699-214X
AD  - University of Helsinki, Faculty of Medicine, Medicum, Department of Virology, 
      Helsinki, Finland.
AD  - University of Zurich, Vetsuisse Faculty, Institute of Veterinary Pathology, 
      Zurich, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220707
PL  - United States
TA  - Microbiol Spectr
JT  - Microbiology spectrum
JID - 101634614
SB  - IM
MH  - Animals
MH  - *Arenaviridae/genetics
MH  - *Boidae
MH  - Cell Line
MH  - *Chiroptera
MH  - *Coinfection
MH  - *Superinfection
PMC - PMC9430581
OTO - NOTNLM
OT  - arenavirus
OT  - cell culture
OT  - coinfection
OT  - persistence
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/22 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/07/07
CRDT- 2022/07/21 16:48
PHST- 2022/07/22 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/07/21 16:48 [entrez]
PHST- 2022/07/07 00:00 [pmc-release]
AID - 01585-22 [pii]
AID - spectrum.01585-22 [pii]
AID - 10.1128/spectrum.01585-22 [doi]
PST - ppublish
SO  - Microbiol Spectr. 2022 Aug 31;10(4):e0158522. doi: 10.1128/spectrum.01585-22. 
      Epub 2022 Jul 7.