Hazara orthonairovirus

In 1954 the Hazara orthonairovirus, one of the 34 tick-borne viruses of the genus Orthonairovirus, was discovered in Pakistan in the Ixodes tick native to that region.[2][3] Today this virus is studied in mice in an attempt to develop treatments for the highly pathogenic Crimean-Congo Hemorrhagic Fever virus.[4]

Hazara orthonairovirus
Virus classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Ellioviricetes
Order: Bunyavirales
Family: Nairoviridae
Genus: Orthonairovirus
Species:
Hazara orthonairovirus
Strains[1]

Characteristics

The Hazara orthonairovirus is part of the genus Orthonairovirus of the Bunyavirales order of viruses, which are an order of enveloped negative-stranded RNA viruses with a genome split into three parts—Small (S), Middle (M) and Large (L). The L RNA segment encodes an RNA-dependent RNA polymerase (L protein), the M RNA segment encodes two surface glycoproteins (Gc and Gn), and the S RNA segment encodes a nucleocapsid protein (N).[5][3] The three genomic RNA segments are encapsidated by copies of the N protein in the form of ribonucleoprotein (RNP) complexes.[6][7] The N protein is the most abundant viral protein in Bunyaviridae virus particles and infected cells and, therefore, the main target in many serological and molecular diagnostics.[8][9]

Transmission

Hazara orthonairovirus is spread by the Ixodes redikorzevi tick. The tick is commonly found on an alpine vole inhabiting the Hazara District of Pakistan.[2]

Signs and symptoms

Hazara orthonairovirus does not cause disease or symptoms in humans. In laboratory mice, symptoms can mirror those of Crimean-Congo Hemorrhagic Fever virus.[4]

Diagnosis

Diagnosis in rodents is made by detecting Hazara orthonairovirus antibodies in the serum.[3]

Clinical importance

Hazara virus is in the same Nairovirus serogroup as Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV), and has similar disease progression to that seen in Crimean-Congo Hemorrhagic Fever (CCHF) infections in suckling mice and in the interferon receptor knockout mouse model [10][4] This indicates that Hazara orthonairovirus could represent a valid model for CCHFV infection.

This finding is particularly important because using the Hazara orthonairovirus (biosafety level 2) as a model allows scientists to investigate this serogroup of viruses for the development of antivirals, without having to work in a biosafety level 4 environment, which is the highest available level of biosecurity, and is mandatory when working with intact CCHFV. While CCHFV is the most important human pathogen in this serogroup, Hazara research is potentially useful in the development of antiviral medications for all viruses in the genus Nairovirus.[7]

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References
  1. Kuhn, Jens H.; et al. (21 September 2016). "Create five (5) new species in the genus Nairovirus(proposed family Nairoviridae, proposed order Bunyavirales), rename the genus Orthonairovirus, and rename all existing species" (PDF). International Committee on Taxonomy of Viruses (ICTV). p. 11. Retrieved 1 April 2019.
  2. Begum, F.; Wisseman Jr., C. L.; Casals, J. (1970). "Tick-borne viruses of the West Pakistan: II. Hazara virus, a new agent isolated from Ixodes redikorzevi ticks from the Kaghan Valley, W. Pakistan12". American Journal of Epidemiology. 92 (3): 192–194. doi:10.1093/oxfordjournals.aje.a121197.
  3. Flusin, O.; Vigne, S.; Peyrefitte, C. N.; Bouloy, M.; Crance, J.-M.; Iseni, F. (2011). "Inhibition of Hazara nairovirus replication by small interfering RNAs and their combination with ribavirin". Virology Journal. 8 (1): 249. doi:10.1186/1743-422X-8-249. PMC 3120786. PMID 21600011.
  4. Dowall, S. D.; Findlay-Wilson, S.; Rayner, E.; Pearson, G.; Pickersgill, J.; Rule, A.; Merredew, N.; Smith, H.; Chamberlain, J.; Hewson, R. (2011). "Hazara virus infection is lethal for adult type I interferon receptor-knockout mice and may act as a surrogate for infection with the human-pathogenic Crimean-Congo hemorrhagic fever virus". Journal of General Virology. 93 (3): 560–564. doi:10.1099/vir.0.038455-0. PMID 22090213.
  5. Crabtree, Mary B.; Sang, Rosemary; Miller, Barry R. (2009). "Kupe Virus, a New Virus in the Family, Genus, Kenya" (PDF). Emerging Infectious Diseases. 15 (2): 147–154. doi:10.3201/eid1502.080851.
  6. Morikawa, S.; Saijo, M.; Kurane, I. (2007). "Recent progress in molecular biology of Crimean–Congo hemorrhagic fever". Comparative Immunology, Microbiology and Infectious Diseases. 30 (5–6): 375–389. doi:10.1016/j.cimid.2007.07.001. PMID 17692916.
  7. Surtees, R.; Ariza, A.; Punch, E. K.; Trinh, C. H.; Dowall, S. D.; Hewson, R.; Hiscox, J. A.; Barr, J. N.; Edwards, T. A. (2015). "The crystal structure of the Hazara virus nucleocapsid protein". BMC Structural Biology. 15: 24. doi:10.1186/s12900-015-0051-3. PMC 4696240. PMID 26715309.
  8. Bilk, S.; Schulze, C.; Fischer, M.; Beer, M.; Hlinak, A.; Hoffmann, B. (2012). "Organ distribution of Schmallenberg virus RNA in malformed newborns". Veterinary Microbiology. 159 (1–2): 236–238. doi:10.1016/j.vetmic.2012.03.035. PMID 22516190.
  9. Bréard, E.; Lara, E.; Comtet, L.; Viarouge, C.; Doceul, V.; Desprat, A.; Vitour, D.; Pozzi, N.; Cay, A. B. (2013). "Validation of a Commercially Available Indirect Elisa Using a Nucleocapside Recombinant Protein for Detection of Schmallenberg Virus Antibodies". PLoS ONE. 8 (1): e53446. Bibcode:2013PLoSO...853446B. doi:10.1371/journal.pone.0053446. PMC 3546048. PMID 23335964.
  10. Bereczky, S.; Lindegren, G.; Karlberg, H.; Åkerström, S.; Klingström, J.; Mirazimi, A. (2010). "Crimean–Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout mice". Journal of General Virology. 91 (6): 1473–1477. doi:10.1099/vir.0.019034-0. PMID 20164263.
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