Enterovirus 68 causes

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Overview

Enterovirus 68 (EV-D68) belongs to the genus enterovirus, serotype D. Its genome consists of a positive-sense ssRNA strand. EV-D68 is acid-labile and has an optimal growth at lower temperatures. Its genome contains one open reading frame (ORF) which encodes for a single polyprotein, that once translated and processed, yields various viral proteins. Viral serotyping is based on a gene (VP1), which encodes 1 of the 4 viral capsid proteins. The viral genome has recently undergone several rearrangements and deletions. Alterations of the untranslated regions (UTR) have led to the classification of the virus into clades. EV-D68 demonstrates tropism for the mucosal cells of the lower respiratory tract, as well as for leukocytes. The virus recognizes Decay-accelerating factor receptor (DAF) and receptors containing sialic-acid on cell surfaces.

Taxonomy

Viruses; ssRNA viruses; ssRNA positive-strand viruses, no DNA stage; Picornavirales; Picornaviridae; Enterovirus; Enterovirus D[1]

Biology

Enterovirus D68 is a non-enveloped, positive-sense ssRNA enterovirus that belongs to the family Picornaviridae.[2] Enteroviruses may be classified according to their antigenic, molecular and biological properties into 4 serotypes of Human Enterovirus (HEV): A, B, C, and D.[3] EV-68 belongs to serotype D, along with EV-D70, EV-D94 and EV-D111. Contrarily to other viruses of the same genus, EV-68 is acid-labile, its replication is optimal at lower temperatures, being more related to rhinoviruses. It commonly causes respiratory disease and has recently been implicated in several outbreaks in Japan, Netherlands, Philippines and in the USA.[3][2][4][5][6] Lower pHs and higher temperatures reduce infectivity titres and viral replication, respectively.[7][8] This ability to survive at lower temperatures is the reason why EV-68 is frequently isolated from respiratory specimens.[9]

Genome

The common genome of an enterovirus is contained within an RNA strand of approximately 7500 nucleotides. It contains one open reading frame (ORF) which encodes for a single polyprotein. Once translated, the polyprotein is processed, yielding different individual viral proteins. Two UTRs flank the ORF polyprotein on both sides, one of which contains an Internal Ribosome Entry Site (IRES).[10]

A gene (VP1), which encodes 1 of the 4 viral capsid proteins, is used to distinguish the different serotypes of enterovirus. Accordingly, the different enteroviruses may be organized in the following serotypes:[11]

  • HEV-A
  • HEV-B
  • HEV-C
  • HEV-D

Serotype specific rabbit antisera are used for typing of EV-68 isolates. Partial sequencing of VP1 capsid gene, using primer 292 (5'-MIGCIGYIGARACNGG-3') and 222 (5'-CICCIGGIGGIAYRWACAT-3') is another method used for sequencing. The serotype is determined by comparing partial sequences of isolates with a database containing partial sequences of all known enterovirus serotypes.[7]

Since 1960, the genome of enterovirus 68 has underwent several rearrangements and deletions, particularly of the UTR, which have led to the classification of the virus into clades. Genomic variations within the IRES region may lead to different effects on virulence, however, in the particular case of EV-68 spacer region, little is known about this impact.[2]

The spacer regions of rhinoviruses are small. It is important to notice that besides sharing cellular tropism for the respiratory epithelium, enterovirus 68 spacer region has been experiencing deletions throughout the years towards the size of the spacer region seen in rhinoviruses. The genome deletions seen in EV-68 may also be responsible for changes in the virulence of the virus, justifying recent outbreaks seen worldwide.[2]

Human rhinovirus 87 was isolated at the same time as EV-68. Corn is a prototype of HRV-87 and is very unique in its receptor quality. Cross neutralization and partial capsid sequence studies revealed that HRV-87 Corn belongs to the same group as EV-68.[12]

Tropism

Unlike other enteroviruses, EV-68 shows tropism for the mucosal cells of the lower respiratory tract, justifying respiratory manifestations that arise from infection.[13] The virus also shows tropism for different leukocyte cell lines, such as: granulocytes; monocytes; B and T lymphocytes.[14] Occasionally, EV-68 may infect the CNS, causing severe complications.[14]

The cellular receptors responsible for the tropism of EV-68 are:[14][15][16]

References

  1. "Enterovirus D68".
  2. 2.0 2.1 2.2 2.3 Tokarz R, Firth C, Madhi SA, Howie SR, Wu W, Sall AA; et al. (2012). "Worldwide emergence of multiple clades of enterovirus 68". J Gen Virol. 93 (Pt 9): 1952–8. doi:10.1099/vir.0.043935-0. PMC 3542132. PMID 22694903.
  3. 3.0 3.1 Oberste MS, Maher K, Schnurr D, Flemister MR, Lovchik JC, Peters H; et al. (2004). "Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses". J Gen Virol. 85 (Pt 9): 2577–84. doi:10.1099/vir.0.79925-0. PMID 15302951.
  4. Hasegawa S, Hirano R, Okamoto-Nakagawa R, Ichiyama T, Shirabe K (2011). "Enterovirus 68 infection in children with asthma attacks: virus-induced asthma in Japanese children". Allergy. 66 (12): 1618–20. doi:10.1111/j.1398-9995.2011.02725.x. PMID 21958204.
  5. Kaida A, Kubo H, Sekiguchi J, Kohdera U, Togawa M, Shiomi M; et al. (2011). "Enterovirus 68 in children with acute respiratory tract infections, Osaka, Japan". Emerg Infect Dis. 17 (8): 1494–7. doi:10.3201/eid1708.110028. PMC 3381549. PMID 21801632.
  6. Jacobson LM, Redd JT, Schneider E, Lu X, Chern SW, Oberste MS; et al. (2012). "Outbreak of lower respiratory tract illness associated with human enterovirus 68 among American Indian children". Pediatr Infect Dis J. 31 (3): 309–12. doi:10.1097/INF.0b013e3182443eaf. PMID 22315004.
  7. 7.0 7.1 Oberste, MS.; Maher, K.; Schnurr, D.; Flemister, MR.; Lovchik, JC.; Peters, H.; Sessions, W.; Kirk, C.; Chatterjee, N. (2004). "Enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses". J Gen Virol. 85 (Pt 9): 2577–84. doi:10.1099/vir.0.79925-0. PMID 15302951. Unknown parameter |month= ignored (help)
  8. Blomqvist, S.; Savolainen, C.; Råman, L.; Roivainen, M.; Hovi, T. (2002). "Human rhinovirus 87 and enterovirus 68 represent a unique serotype with rhinovirus and enterovirus features". J Clin Microbiol. 40 (11): 4218–23. PMID 12409401. Unknown parameter |month= ignored (help)
  9. "Clusters of acute respiratory illness associated with human enterovirus 68--Asia, Europe, and United States, 2008-2010". MMWR Morb Mortal Wkly Rep. 60 (38): 1301–4. 2011. PMID 21956405. Unknown parameter |month= ignored (help)
  10. Fields, Bernard (2001). Fields virology. Philadelphia: Lippincott Williams & Wilkins. ISBN 0781718325.
  11. Oberste MS, Maher K, Kilpatrick DR, Pallansch MA (1999). "Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification". J Virol. 73 (3): 1941–8. PMC 104435. PMID 9971773.
  12. Ishiko, H.; Miura, R.; Shimada, Y.; Hayashi, A.; Nakajima, H.; Yamazaki, S.; Takeda, N. (2002). "Human rhinovirus 87 identified as human enterovirus 68 by VP4-based molecular diagnosis". Intervirology. 45 (3): 136–41. doi:65866 Check |doi= value (help). PMID 12403917.
  13. Renois F, Bouin A, Andreoletti L (2013). "Enterovirus 68 in pediatric patients hospitalized for acute airway diseases". J Clin Microbiol. 51 (2): 640–3. doi:10.1128/JCM.02640-12. PMC 3553905. PMID 23224095.
  14. 14.0 14.1 14.2 Smura T, Ylipaasto P, Klemola P, Kaijalainen S, Kyllönen L, Sordi V; et al. (2010). "Cellular tropism of human enterovirus D species serotypes EV-94, EV-70, and EV-68 in vitro: implications for pathogenesis". J Med Virol. 82 (11): 1940–9. doi:10.1002/jmv.21894. PMID 20872722.
  15. Vlasak M, Roivainen M, Reithmayer M, Goesler I, Laine P, Snyers L; et al. (2005). "The minor receptor group of human rhinovirus (HRV) includes HRV23 and HRV25, but the presence of a lysine in the VP1 HI loop is not sufficient for receptor binding". J Virol. 79 (12): 7389–95. doi:10.1128/JVI.79.12.7389-7395.2005. PMC 1143622. PMID 15919894.
  16. Savolainen-Kopra C, Blomqvist S, Kaijalainen S, Jounio U, Juvonen R, Peitso A; et al. (2009). "All known human rhinovirus species are present in sputum specimens of military recruits during respiratory infection". Viruses. 1 (3): 1178–89. doi:10.3390/v1031178. PMC 3185535. PMID 21994588.