Characterization of Haartman Institute snake virus-1 (HISV-1) and HISV-like viruses-The representatives of genus Hartmanivirus, family Arenaviridae

PLoS Pathog. 2018 Nov 14;14(11):e1007415. doi: 10.1371/journal.ppat.1007415. eCollection 2018 Nov.

Abstract

The family Arenaviridae comprises three genera, Mammarenavirus, Reptarenavirus and the most recently added Hartmanivirus. Arenaviruses have a bisegmented genome with ambisense coding strategy. For mammarenaviruses and reptarenaviruses the L segment encodes the Z protein (ZP) and the RNA-dependent RNA polymerase, and the S segment encodes the glycoprotein precursor and the nucleoprotein. Herein we report the full length genome and characterization of Haartman Institute snake virus-1 (HISV-1), the putative type species of hartmaniviruses. The L segment of HISV-1 lacks an open-reading frame for ZP, and our analysis of purified HISV-1 particles by SDS-PAGE and electron microscopy further support the lack of ZP. Since we originally identified HISV-1 in co-infection with a reptarenavirus, one could hypothesize that co-infecting reptarenavirus provides the ZP to complement HISV-1. However, we observed that co-infection does not markedly affect the amount of hartmanivirus or reptarenavirus RNA released from infected cells in vitro, indicating that HISV-1 does not benefit from reptarenavirus ZP. Furthermore, we succeeded in generating a pure HISV-1 isolate showing the virus to replicate without ZP. Immunofluorescence and ultrastructural studies demonstrate that, unlike reptarenaviruses, HISV-1 does not produce the intracellular inclusion bodies typical for the reptarenavirus-induced boid inclusion body disease (BIBD). While we observed HISV-1 to be slightly cytopathic for cultured boid cells, the histological and immunohistological investigation of HISV-positive snakes showed no evidence of a pathological effect. The histological analyses also revealed that hartmaniviruses, unlike reptarenaviruses, have a limited tissue tropism. By nucleic acid sequencing, de novo genome assembly, and phylogenetic analyses we identified additional four hartmanivirus species. Finally, we screened 71 individuals from a collection of snakes with BIBD by RT-PCR and found 44 to carry hartmaniviruses. These findings suggest that harmaniviruses are common in captive snake populations, but their relevance and pathogenic potential needs yet to be revealed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae / genetics
  • Arenaviridae Infections / virology
  • Arenavirus / classification*
  • Arenavirus / genetics*
  • Base Sequence
  • Boidae / virology
  • Cell Line
  • Inclusion Bodies, Viral / pathology
  • Phylogeny
  • RNA, Viral / genetics
  • RNA-Dependent RNA Polymerase / genetics
  • Viral Proteins / genetics

Substances

  • RNA, Viral
  • Viral Proteins
  • RNA-Dependent RNA Polymerase

Grants and funding

The authors received funding for this work from the following institutions: Academy of Finland (www.aka.fi/, grant numbers 1308613 and 1314119 to JH), Jenny and Antti Wihuri foundation (https://wihurinrahasto.fi/ to JH), and Schweizerische Vereinigung fuer Wild-, Zoo- und Heimtiermedizin (to "BIBD group"). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.