1887

Abstract

The Nairoviridae family within the Bunyavirales order comprise tick-borne segmented negative-sense RNA viruses that cause serious disease in a broad range of mammals, yet cause a latent and lifelong infection in tick hosts. An important member of this family is Crimean-Congo haemorrhagic fever virus (CCHFV), which is responsible for serious human disease that results in case fatality rates of up to 30 %, and which exhibits the most geographically broad distribution of any tick-borne virus. Here, we explored differences in the cellular response of both mammalian and tick cells to nairovirus infection using Hazara virus (HAZV), which is a close relative of CCHFV within the CCHFV serogroup. We show that HAZV infection of human-derived SW13 cells led to induction of apoptosis, evidenced by activation of cellular caspases 3, 7 and 9. This was followed by cleavage of the classical apoptosis marker poly ADP-ribose polymerase, as well as cellular genome fragmentation. In addition, we show that the HAZV nucleocapsid (N) protein was abundantly cleaved by caspase 3 in these mammalian cells at a conserved DQVD motif exposed at the tip of its arm domain, and that cleaved HAZV-N was subsequently packaged into nascent virions. However, in stark contrast, we show for the first time that nairovirus infection of cells of the tick vector failed to induce apoptosis, as evidenced by undetectable levels of cleaved caspases and lack of cleaved HAZV-N. Our findings reveal that nairoviruses elicit diametrically opposed cellular responses in mammalian and tick cells, which may influence the infection outcome in the respective hosts.

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2019-02-05
2019-08-22
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References

  1. Lasecka L, Baron MD. The molecular biology of nairoviruses, an emerging group of tick-borne arboviruses. Arch Virol 2014;159:1249–1265 [CrossRef][PubMed]
    [Google Scholar]
  2. Al-Tikriti SK, Al-Ani F, Jurji FJ, Tantawi H, Al-Moslih M et al. Congo/crimean haemorrhagic fever in Iraq. Bull World Health Organ 1981;59:85–90[PubMed]
    [Google Scholar]
  3. Papa A, Christova I, Papadimitriou E, Antoniadis A. Crimean-congo hemorrhagic fever in Bulgaria. Emerg Infect Dis 2004;10:1465–1467 [CrossRef][PubMed]
    [Google Scholar]
  4. Nabeth P, Cheikh DO, Lo B, Faye O, Vall IO et al. Crimean-congo hemorrhagic fever, Mauritania. Emerg Infect Dis 2004;10:2143–2149 [CrossRef][PubMed]
    [Google Scholar]
  5. Begum F, Wisseman CL, Casals J. Tick-borne viruses of West Pakistan. II. Hazara virus, a new agent isolated from Ixodes redikorzevi ticks from the Kaghan Valley, W. Pakistan. Am J Epidemiol 1970;92:192–194 [CrossRef][PubMed]
    [Google Scholar]
  6. Okorie TG. Comparative studies on the vector capacity of the different stages of amblyomma variegatum fabricius and hyalomma rufipes koch for congo virus, after intracoelomic inoculation. Vet Parasitol 1991;38:215–223 [CrossRef][PubMed]
    [Google Scholar]
  7. Smirnova SE. A comparative study of the crimean hemorrhagic fever-congo group of viruses. Arch Virol 1979;62:137–143 [CrossRef][PubMed]
    [Google Scholar]
  8. Dowall SD, Findlay-Wilson S, Rayner E, Pearson G, Pickersgill J et al. 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. J Gen Virol 2012;93:560–564 [CrossRef][PubMed]
    [Google Scholar]
  9. Whitehouse CA. Crimean-congo hemorrhagic fever. Antiviral Res 2004;64:145–160 [CrossRef][PubMed]
    [Google Scholar]
  10. Morikawa S, Saijo M, Kurane I. “Recent progress in molecular biology of crimean-congo hemorrhagic fever”. Comp Immunol Microbiol Infect Dis 302007;6:375–389
    [Google Scholar]
  11. Wang W, Liu X, Wang X, Dong H, Ma C et al. Structural and functional diversity of nairovirus-encoded nucleoproteins. J Virol 2015;89:11740–11749 [CrossRef][PubMed]
    [Google Scholar]
  12. Carter SD, Surtees R, Walter CT, Ariza A, Bergeron É et al. Structure, function, and evolution of the crimean-congo hemorrhagic fever virus nucleocapsid protein. J Virol 2012;86:10914–10923 [CrossRef][PubMed]
    [Google Scholar]
  13. Qi X, Lan S, Wang W, Schelde LM, Dong H et al. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature 2010;468:779–783 [CrossRef][PubMed]
    [Google Scholar]
  14. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495–516 [CrossRef][PubMed]
    [Google Scholar]
  15. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science 1998;281:1305–1308 [CrossRef][PubMed]
    [Google Scholar]
  16. Ho PK, Hawkins CJ. Mammalian initiator apoptotic caspases. FEBS J 2005;272:5436–5453 [CrossRef][PubMed]
    [Google Scholar]
  17. Thomson BJ. Viruses and apoptosis. Int J Exp Pathol 2001;82:65–76 [CrossRef][PubMed]
    [Google Scholar]
  18. Zhou Q, Krebs JF, Snipas SJ, Price A, Alnemri ES et al. Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex. Biochemistry 1998;37:10757–10765 [CrossRef][PubMed]
    [Google Scholar]
  19. Kohl A, Clayton RF, Weber F, Bridgen A, Randall RE et al. Bunyamwera virus nonstructural protein NSs counteracts interferon regulatory factor 3-mediated induction of early cell death. J Virol 2003;77:7999–8008 [CrossRef][PubMed]
    [Google Scholar]
  20. Acrani GO, Gomes R, Proença-Módena JL, da Silva AF, Oliveira Carminati P et al. “Apoptosis induced by oropouche virus infection in HeLa cells is dependent on virus protein expression,”. Virus Res 2010;468:779–783
    [Google Scholar]
  21. Blakqori G, Delhaye S, Habjan M, Blair CD, Sánchez-Vargas I et al. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J Virol 2007;81:4991–4999 [CrossRef][PubMed]
    [Google Scholar]
  22. Bell-Sakyi L. Continuous cell lines from the tick hyalomma anatolicum anatolicum. J Parasitol 1991;77:1006–1008 [CrossRef][PubMed]
    [Google Scholar]
  23. Punch EK, Hover S, Blest HTW, Fuller J, Hewson R et al. Potassium is a trigger for conformational change in the fusion spike of an enveloped RNA virus. J Biol Chem 2018;293:9937–9944 [CrossRef][PubMed]
    [Google Scholar]
  24. Surtees R, Ariza A, Punch EK, Trinh CH, Dowall SD et al. The crystal structure of the hazara virus nucleocapsid protein. BMC Struct Biol 2015;15:24 [CrossRef][PubMed]
    [Google Scholar]
  25. Surtees R, Dowall SD, Shaw A, Armstrong S, Hewson R et al. Heat shock protein 70 family members interact with crimean-congo hemorrhagic fever virus and hazara virus nucleocapsid proteins and perform a functional role in the nairovirus replication cycle. J Virol 2016;90:9305–9316 [CrossRef][PubMed]
    [Google Scholar]
  26. Barnwal B, Karlberg H, Mirazimi A, Tan YJ. The non-structural protein of crimean-congo hemorrhagic fever virus disrupts the mitochondrial membrane potential and induces apoptosis. J Biol Chem 2016;291:582–592 [CrossRef][PubMed]
    [Google Scholar]
  27. Kyrylkova K, Kyryachenko S, Leid M, Kioussi C. Detection of apoptosis by TUNEL assay. Methods Mol Biol 2012;887:41–47 [CrossRef][PubMed]
    [Google Scholar]
  28. Wolff S, Becker S, Groseth A. Cleavage of the Junin virus nucleoprotein serves a decoy function to inhibit the induction of apoptosis during infection. J Virol 2013;87:224–233 [CrossRef][PubMed]
    [Google Scholar]
  29. Schotte P, Declercq W, van Huffel S, Vandenabeele P, Beyaert R. Non-specific effects of methyl ketone peptide inhibitors of caspases. FEBS Lett 1999;442:117–121 [CrossRef][PubMed]
    [Google Scholar]
  30. Hoogstraal H. The epidemiology of tick-borne Crimean-congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol 1979;15:307–417 [CrossRef][PubMed]
    [Google Scholar]
  31. Papa A, Tsergouli K, Tsioka K, Mirazimi A. Crimean-congo hemorrhagic fever: tick-host-virus interactions. Front Cell Infect Microbiol 2017;7:213 [CrossRef][PubMed]
    [Google Scholar]
  32. Rodrigues R, Paranhos-Baccalà G, Vernet G, Peyrefitte CN. Crimean-congo hemorrhagic fever virus-infected hepatocytes induce ER-stress and apoptosis crosstalk. PLoS One 2012;7:e29712 [CrossRef][PubMed]
    [Google Scholar]
  33. Hewson R, Chamberlain J, Mioulet V, Lloyd G, Jamil B et al. Crimean-congo haemorrhagic fever virus: sequence analysis of the small RNA segments from a collection of viruses world wide. Virus Res 2004;102:185–189 [CrossRef][PubMed]
    [Google Scholar]
  34. Pekosz A, Phillips J, Pleasure D, Merry D, Gonzalez-Scarano F. Induction of apoptosis by La Crosse virus infection and role of neuronal differentiation and human bcl-2 expression in its prevention. J Virol 1996;70:5329–5335[PubMed]
    [Google Scholar]
  35. Hacker D, Raju R, Kolakofsky D. La Crosse virus nucleocapsid protein controls its own synthesis in mosquito cells by encapsidating its mRNA. J Virol 1989;63:5166–5174[PubMed]
    [Google Scholar]
  36. Newton SE, Short NJ, Dalgarno L. Bunyamwera virus replication in cultured Aedes albopictus (mosquito) cells: establishment of a persistent viral infection. J Virol 1981;38:1015–1024[PubMed]
    [Google Scholar]
  37. Zhirnov OP, Syrtzev VV. Influenza virus pathogenicity is determined by caspase cleavage motifs located in the viral proteins. J Mol Genet Med 2009;3:124–132 [CrossRef][PubMed]
    [Google Scholar]
  38. Wang Y, Dutta S, Karlberg H, Devignot S, Weber F et al. Structure of crimean-congo hemorrhagic fever virus nucleoprotein: superhelical homo-oligomers and the role of caspase-3 cleavage. J Virol 2012;86:12294–12303 [CrossRef][PubMed]
    [Google Scholar]
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