Chikungunya virus

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Chikungunya.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Chikungunya virus is an alphavirus with a positive sense single-stranded RNA genome of approximately 11.6kb. It is a member of the Semliki Forest Virus complex and is closely related to Ross River Virus, O’Nyong Nyong virus and Semliki Forest Virus.[1] In the United States it is classified as a Category C priority pathogen[2] and work requires Biosafety Level 3 precautions.[3] Human epithelial, endothelial, primary fibroblasts and monocyte-derived macrophages are permissive for chikungunya virus in vitro and viral replication is highly cytopathic but susceptible to type I and II interferon.[4] In vivo, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells and myofibers.[5][6]

Virology

Chikungunya virus
Cryoelectron microscopy reconstruction of chikungunya virus.
Cryoelectron microscopy reconstruction of chikungunya virus.
Virus classification
Group: Group IV ((+)ssRNA)
Order: Unassigned
Family: Togaviridae
Genus: Alphavirus
Species: Chikungunya virus

Chikungunya virus is an alphavirus with a positive sense single-stranded RNA genome of approximately 11.6kb. It is a member of the Semliki Forest Virus complex and is closely related to Ross River Virus, O’Nyong Nyong virus and Semliki Forest Virus.[7] In the United States it is classified as a Category C priority pathogen[8] and work requires Biosafety Level 3 precautions.[9]

Human epithelial, endothelial, primary fibroblasts and monocyte-derived macrophages are permissive for chikungunya virus in vitro and viral replication is highly cytopathic but susceptible to type I and II interferon.[10] In vivo, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells and myofibers.[5][11][12]

Type 1 interferon

Upon infection with chikungunya, the host's fibroblasts produce type 1 (alpha and beta) interferon.[13] Mice that lack the interferon alpha receptor die in 2–3 days after exposure to 102 chikungunya PFU, while wild type mice survive even when exposed to as much as 106 PFU of the virus.[13] At the same time, mice that are partially type 1 interferon deficient (IFN α/β +/−) are mildly affected and experience symptoms such as muscle weakness and lethargy.[14] Partidos et al. 2011 saw similar results with the live attenuated strain CHIKV181/25. However, rather than dying, the type 1 interferon deficient (IFN α/β −/−) mice were temporarily disabled and the partially type 1 interferon deficient mice did not have any problems.[15]

Several studies have attempted to find the upstream components of the type 1 interferon pathway involved in the host's response to chikungunya infection. So far, no one knows the chikungunya specific pathogen associated molecular pattern.[16] Nonetheless, IPS-1 (IFN-β promoter stimulator 1)—also known as Cardiff, MAVS (mitochondrial antiviral signaling protein), and VISA (virus-induced signaling adapter)—has been found to be an important factor. In 2011, White et al. found that interfering with IPS-1 decreased the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of IFN-β.[16] Other studies have found that IRF3 and IRF7 are important in an age-dependent manner. Adult mice that lack both of these regulatory factors die upon infection with chikungunya.[17] Neonates, on the other hand, succumb to the virus if they are deficient in one of these factors.[18]

Chikungunya counters the type 1 interferon response by producing NS2, a non-structural protein that degrades Rpb and turns off the host cell's ability to transcribe DNA.[19] NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated.[20]

Gallery

  • Transmission electron micrograph (TEM) depicts numerous Chikungunya virus particles. From Public Health Image Library (PHIL). [21]

    Transmission electron micrograph (TEM) depicts numerous Chikungunya virus particles. From Public Health Image Library (PHIL). [21]

  • At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia From Public Health Image Library (PHIL). [21]

    At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia From Public Health Image Library (PHIL). [21]

  • At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. From Public Health Image Library (PHIL). [21]

    At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. From Public Health Image Library (PHIL). [21]

  • Magnified 1500X, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. From Public Health Image Library (PHIL). [21]

    Magnified 1500X, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. From Public Health Image Library (PHIL). [21]

References

  1. ↑ Powers, AM (Nov 2001). "Evolutionary relationships and systematics of the alphaviruses". Journal of Virology. 75 (21): 10118–31. doi:10.1128/JVI.75.21.10118-10131.2001. PMC 114586. PMID 11581380. Unknown parameter |coauthors= ignored (help)
  2. ↑ "NIAID Category A, B, and C Priority Pathogens". Retrieved 1 January 2014.
  3. ↑ "Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition" (PDF). Retrieved 1 January 2014.
  4. ↑ Sourisseau, M (Jun 2007). "Characterization of reemerging chikungunya virus". PLoS Pathogens. 3 (6): e89. doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450. Unknown parameter |coauthors= ignored (help)
  5. ↑ 5.0 5.1 Schilte, C (Feb 15, 2010). "Type I IFN controls chikungunya virus via its action on nonhematopoietic cells". The Journal of experimental medicine. 207 (2): 429–42. doi:10.1084/jem.20090851. PMC 2822618. PMID 20123960. Unknown parameter |coauthors= ignored (help)
  6. ↑ Rohatgi, A (Dec 11, 2013). "Infection of myofibers contributes to the increased pathogenicity during infection with an epidemic strain of Chikungunya Virus". Journal of Virology. 88 (5): 2414–25. doi:10.1128/JVI.02716-13. PMID 24335291. Unknown parameter |coauthors= ignored (help)
  7. ↑ Powers, AM (Nov 2001). "Evolutionary relationships and systematics of the alphaviruses". Journal of Virology. 75 (21): 10118–31. doi:10.1128/JVI.75.21.10118-10131.2001. PMC 114586. PMID 11581380. Unknown parameter |coauthors= ignored (help)
  8. ↑ "NIAID Category A, B, and C Priority Pathogens". Retrieved 1 January 2014.
  9. ↑ "Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition" (PDF). Retrieved 1 January 2014.
  10. ↑ Sourisseau, M (Jun 2007). "Characterization of reemerging chikungunya virus". PLoS Pathogens. 3 (6): e89. doi:10.1371/journal.ppat.0030089. PMC 1904475. PMID 17604450. Unknown parameter |coauthors= ignored (help)
  11. ↑ Schilte, C (Feb 15, 2010). "Type I IFN controls chikungunya virus via its action on nonhematopoietic cells". The Journal of experimental medicine. 207 (2): 429–42. doi:10.1084/jem.20090851. PMC 2822618. PMID 20123960. Unknown parameter |coauthors= ignored (help)
  12. ↑ Rohatgi, A (Dec 11, 2013). "Infection of myofibers contributes to the increased pathogenicity during infection with an epidemic strain of Chikungunya Virus". Journal of Virology. 88 (5): 2414–25. doi:10.1128/JVI.02716-13. PMID 24335291. Unknown parameter |coauthors= ignored (help)
  13. ↑ 13.0 13.1 Schilte C, Couderc T, Chretien F; et al. (February 2010). "Type I IFN controls chikungunya virus via its action on nonhematopoietic cells". J. Exp. Med. 207 (2): 429–42. doi:10.1084/jem.20090851. PMC 2822618. PMID 20123960.
  14. ↑ Couderc T, Chrétien F, Schilte C; et al. (February 2008). "A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease". PLoS Pathog. 4 (2): e29. doi:10.1371/journal.ppat.0040029. PMC 2242832. PMID 18282093.
  15. ↑ Partidos CD, Weger J, Brewoo J; et al. (April 2011). "Probing the attenuation and protective efficacy of a candidate chikungunya virus vaccine in mice with compromised interferon (IFN) signaling". Vaccine. 29 (16): 3067–73. doi:10.1016/j.vaccine.2011.01.076. PMC 3081687. PMID 21300099.
  16. ↑ 16.0 16.1 White LK, Sali T, Alvarado D; et al. (January 2011). "Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff". J. Virol. 85 (1): 606–20. doi:10.1128/JVI.00767-10. PMC 3014158. PMID 20962078.
  17. ↑ Rudd PA, Wilson J, Gardner J; et al. (September 2012). "Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock". J. Virol. 86 (18): 9888–98. doi:10.1128/JVI.00956-12. PMC 3446587. PMID 22761364.
  18. ↑ Schilte C, Buckwalter MR, Laird ME, Diamond MS, Schwartz O, Albert ML (April 2012). "Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection". J. Immunol. 188 (7): 2967–71. doi:10.4049/jimmunol.1103185. PMID 22371392.
  19. ↑ Akhrymuk I, Kulemzin SV, Frolova EI (July 2012). "Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II". J. Virol. 86 (13): 7180–91. doi:10.1128/JVI.00541-12. PMC 3416352. PMID 22514352.
  20. ↑ Fros JJ, Liu WJ, Prow NA; et al. (October 2010). "Chikungunya virus nonstructural protein 2 inhibits type I/II interferon-stimulated JAK-STAT signaling". J. Virol. 84 (20): 10877–87. doi:10.1128/JVI.00949-10. PMC 2950581. PMID 20686047.
  21. ↑ 21.0 21.1 21.2 21.3 "Public Health Image Library (PHIL)".
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