Norovirüsün genomik yapısı, replikasyonu ve epidemiyolojisi

Norovirüs çocuklarda ve yetişkinlerde yaygın olarak sporadik gastroenteritlere veya gıda ve su kaynaklı salgınlara neden olan bir RNA virüsüdür. Genomik organizasyonu yapısal ve yapısal olmayan proteinleri kodlayan ORF1, ORF2 ve ORF3 olmak üzere üç açık okuma bölgesi [open reading frame (ORF)] içermektedir. ORF1, yapısal olmayan poliproteini kodlarken; ORF2 yapısal majör kapsid proteini VP1'i, ORF3 ise yapısal VP2 proteinini kodlamaktadır. Norovirüsler nükleotid dizi benzerliğine göre beş genogruba ayrılmaktadır. İnsanları infekte eden genogruplar GI, GII ve GIV'tür. GIII genogrubu sığır türlerini, GV genogrubu ise fare türlerini infekte etmektedir. Norovirüsün replikasyonu virüsün in vitro koşullarda kültürü yapılamadığı için henüz tam olarak aydınlatılamasa da hayvanları infekte eden diğer genogrupların kültürleri kullanılarak çeşitli çalışmalar yürütülmektedir. Dünyada ve Türkiye'de, norovirüs her yaş grubundan insanı infekte edebildiği gibi; daha çok çocuklar ve yaşlıların yaşadığı topluluklarda salgınlara neden olmaktadır. Bu salgınların çoğundan GII, özellikle de GII.4 genotipinin suşları sorumludur. GII genogrubunu, GI suşları izlemekte, GIV ise daha az oranda görülmektedir. Türkiye'de 2008 yılında meydana gelen salgında da GI ve GII genogrupları saptanmıştır. Ülkemizde norovirüs ile ilgili yapılan az sayıdaki çalışmada da GII genogrubuna daha sık rastlanmıştır. Özellikle akut gastroenteritli çocukların dahil edildiği araştırmalar öne çıkmakta ve yaklaşık %10-17 oranında norovirüs pozitifliği saptanmaktadır. Norovirüsün laboratuvar tanısında, genogrupların tayini ve virüsün tiplendirilebilmesi için altın standart, revers transkriptaz-polimeraz zincir reaksiyonudur, ancak hızlı tanı için daha çok ELISA ve immünkromatografik çabuk tanı testleri kullanılmaktadır.
Anahtar Kelimeler:

Genomik, Epidemiyoloji, Norovirus

Genomic structure, replication and epidemiology of norovirus

Norovirus is an RNA virus that causes commonly sporadic gastroenteritis or foodborne and waterborne outbreaks in children and adults. Its genomic organization includes three open reading frames (ORF) ORF1, ORF2 and ORF3 which encode the structural and the non-structural proteins. ORF1 encodes the non-structural polyprotein, ORF2 encodes VP1 which is the structural major capsid protein and ORF3 encodes structural protein VP2. Noroviruses are subdivided into five genogroups according to the nucleotide sequence similarity. Genogroups infecting humans are GI, GII and GIV. Genogroup GIII infects bovine species, genogroup GV infects murine species. Due to the lack of an in vitro culture system, noroviruses replication is not elucidated, however several studies are carried out using the culture of other genogroups infecting animals. Around the world and in Turkey as well as norovirüs can infect every age groups of people, outbreaks commonly occur in communities containing rather children and elderly population. Genogroup II and especially genotype GII.4 strains are responsible from the bulk of these outbreaks. Genogroup II is followed by GI and GIV is seen less common. GI and GII genogroups were detected in an outbreak that occurred in Turkey in 2008. In a few studies had been carried out about norovirus in our country genogroup GII is detected more often. Especially, studies involved children with acute gastroenteritis are prominent and approximately 10-17% norovirüs positivity is detected. In the laboratory diagnosis of noroviruses reverse transcriptase-polymerase chain reaction is the gold standard to determine the genogroups, however ELISA and immunochromatographic rapid diagnostic tests are in common use for quick results.

Kaynakça

1. Thornton AC, jennings-Conklin KS, McCormick MI. Norovi-ruses: agents in outbreaks of acute gastroenteritis. Disaster Manage Response 2004;2:4-9.

2. Ustaçeiebi Ş, Abacıoğlu H, Badur S. Norwaik virus. Ustaçe-iebi Ş, Abacıoğlu H, Badur S (editörler). Moleküler, Klinik ve Tanısal Viroloji. 1. Baskı. Ankara: Güneş Kitabevi, 2004: 249-53.

3. Koo HL, Ajami N, Atmar RL, Dupont HL. Noroviruses: the principal cause of foodborne disease worldwide. Discov Med 2010;10:61-70.

4. Siebenga J}, Vennema H, Zheng DP, Vinje ), Lee BE, Pang XL, et al. Norovirus illness is a global problem: emergence and spread of norovirus G 11.4 variants, 2001-2007. J Infect Dis 2009;200:802-12.

5. Mladenova Z, Korsun N, Ceonova T, Di Bartolo I, Fiore L, Ruggeri FM, et al. Prevalence and molecular epidemiology of noroviruses detected in outbreak and sporadic cases of gcu-te gastroenteritis in Bulgaria. ] Med Virol 2008;80:2161-8.

6. Atmar RL, Estes MK. Diagnosis of noncultivatable gastroenteritis viruses, the human caliciviruses. Clin Microbiol Rev 2001;1:15-37,

7. Rabenau HF, Stürmer M, Buxbaum S, Walczok A, Preiser W, Doerr HW. Laboratory diagnosis of norovirus: Which method is the best? Intervirology 2003;46:232-8.

8. Bruin E, Duizer E, Vennema H, Koopmans MPC. Diagnosis of norovirus outbreaks by commercial ELISA or RT-PCR. j Virol Methods 2006; 137:259-64.

9. Vipond IB, Pelosi E, Williams I, Ashley CR, Lambden PR, Clarke IN, et al. A diagnostic EIA for detection of the prevalent SRSV strain in United Kingdom outbreaks of gastroenteritis. ) Med Virol 2000;61:132-7.

10. Richards CP, Watson MA, Fankhauser RL, Monroe SS. Ge-nogroup I and II noroviruses detected in stool samples by real-time reverse transcription-PCR using highly degenerate universal primers., Appl Environ Microbiol 2004;70:7179-84.

11. Mohamed N, Belak S, Hedlund KO, Blomberg j. Experience from the development of a diagnostic single tube real-time PCR for human caliciviruses, norovirus genogroups I and II. J Virol Methods 2006;132:69-76.

12. Donaldson EF, Lindesmith LC, Lobue AD, Baric RS. Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations. Immunol Rev 2008;225:190-11.

13. Tan M, Fang P, Chachiyo T, Xia M, Huang P, Fang Z, et al. Noroviral P particle: structure, function and applications in virus-host interaction. Virology 2008;382:115-23.

14. Bull RA, White PA. Mechanisms of C 11.4 norovirus evolution. Trends Microbiol 2011;5:233-40.

15. Prasad BV, Hardy ME, Dokland T, Bella J, Rossmann MC, Es-tes MK. X-ray crystallographic structure of the norwalk virus capsid. Science 1999;286:287-90.

16. Rohayem J, Bergmann M, Gebhardt j, Could E, Tucker P, Mattevi A, et al. Antiviral strategies to control calicivirus infections. Antiviral Research 2010;87:162-78.

17. Asanaka M, Atmar RL, Ruvolo V, Crawford SE, Neill FH, Es-tes MK. Replication and packaging of Norwalk virus RNA in cultured mammalian cells. PNAS 2005;29:10327-32.

18. Kapikian AZ. The discovery of the 27-nm NV: an historic perspective. J Infect Dis 2000;181(Suppl):295-302.

19. Cuix S, Asanaka M, Katayama K, Crawford SE, Neill FH, Atmar RL, et al. Norwalk virus RNA is infectious in mammalian cells. J Virol 2007;81:12238-48.

20. Straub TM, Höner zu Bentrup K, Orosz-Coghlan P, Dohnal-kova A, Mayer BK, Bartholomew RA, et al. In vitro cell culture infectivity assay for human noroviruses. Emerg Infect Dis 2007;13:396-403.

21. Pate! MM, Widdowson MA, Class Rl, Akazawa K, Vinje J, Parashar UD. Systematic literature review of role of noroviruses in sporadic gastroenteritis. Emerg Infect Dis 2008;8:1224-31.

22. Lopman BA, Reacher M, Callimore C, Adak CK, Cray Jj, Brown DWG. A summertime peak of winter vomiting disease: surveillance of noroviruses in England and Wales, 1995 to 2002. BMC Public Health 2003 (http://www.biomed-central.com/1471-2458/3/13).

23. Centers for Disease Control and Prevention, 2009. Surveillance for food borne disease outbreaks-United States. MMWR 2006;58:609-15.

24. Akçalı A, Esen B. Norovirus Outbreaks in Some European Countries. AER 2005;4:150-1.

25. Vega E, Vinje J. Novel Gil. 12 Norovirus Strain, United States, 2009-2010. Emerg Infect Dis 2011;17:1516-8.

26. Ferreira MSR, Victoria M, Carvalho-Costa FA, Vieira CB, Xa-vier MPTP, Fioretti JM, et al. Surveillance of Norovirus Infections in the State of Rio De Janeiro, Brazil 2005-2008. j Med Virol 2010;82:1442-8.

27. Morillo SG, Lunch s A, Cilli A, Ribeiro CD, Calux S], Carmo-na RCC, et al. Large gastroenteritis outbreak due to norovirus Cll in Sao Paulo, Brazil, summer 2010 (Letter to Editor). Rev Inst Med Trop Sao Paulo 2011;53:119-20.

28. O'Ryan ML, Pena A, Vergara R, Diaz J, Mamani N, Cortes H, et al. Prospective characterization of norovirus compared with rotavirus acute diarrhea episodes in Chilean children. Pediatr Infect Dis J 2010;29:855-9.

29. O'Ryan ML, Lucero Y, Prado V, Santolaya ME, Rabello M, Solis Y, et al. Symptomatic and asymptomatic rotavirus and norovirus infections during infancy in a Chilean birth cohort. Pediatr Infect Dis J 2009;28:879-84.

30. Siebenga JJ, Vennema H, Duizer E, Koopmans MPG. Gastroenteritis caused by norovirus GGU.4, the Netherlands, 1994-2005. Emerg Infect Dis 2007;13:144-6.

31. Falkanhorst C, Krusell L, Lisby M, Madsen SB, Böttiger B, Molbak K, et al. Imported frozen raspberries cause a series of norovirus outbreaks in Denmark, 2005. Eurosurveillance 2005;10:2795.

32. Schmid D, Lederer I, Much P, Pichler AM, Allerberger F. Outbreak of norovirus infection associated with contaminated flood water, Salzburg, 2005. Eurosurveillance 2005;10:2727.

33. Terletskaia-Ladwig E, Eggers M, Enders M, Regnath T. Epidemiological aspects of gastrointestinal infections. Dtsch Med Wochenschr 2011;136:69-75.

34. Apelt N, Hartberger C, Campe H, Löscher T. The Prevalence of Norovirus in returning international travelers with diarrhea, BMC Infect Dis 2010;10:131.

35. Domenech-Sanchez A. Gastroenteritis outbreak caused by norovirus associated with the children's club of a hotel located in Majorca, Spain. Clin Microbiol Infect 2011 ;17:949-51.

36. Phillips G, Tam CC, Conti S, Rodrigues LC, Brown D, Iturri-za-Gomara M, et al. Community Incidence of norovirus-as-sociated infectious intestinal disease in england: improved estimates using viral load for norovirus diagnosis. Am J Epidemiol 2010;171:1014-22.

37. van Asten L, Siebenga J, van den Wijngaard C, Verheij R, van Vliet H, Kretzschmar M, et al. Unspecified gastroenteritis illness and deaths in the elderly associated with norovirus epidemics. Epidemiology 2011;22:336-43.

38. Kele B, Lengyel G, Deak J. Comparison of an ELISA and two reverse transcription PCR methods for norovirus detection. Diagn Microbiol Infect Dis 2011;70:475-8.

39. Dai Y, Hu G, Zhang X, Song C, Xiang W, Wu X, et al. Molecular epidemiology of norovirus gastroenteritis in children in Jiangmen, China, 2005-2007. Arch Virol2011;l56:164l-6.

40. Jin M, Sun \L, Çhang ZR, Li HY, Liu N, Zhang Q, et al. Outbreaks of noroviral gastroenteritis and their molecular characteristics in China, 2006-2007. Zhonghua Liu Xing Bing Xue Za Zhi 2010;31:549-53.

41. CaoY, Jin M, Cong X, Duan Z, Li HY, Cuo X, et al. Clinical and molecular epidemiologic analyses of norovirus-associ-ated sporadic gastroenteritis in adults from Beijing, China. J Med Virol 2011;83:1078-85.

42. Zeng M, Chen j, Gong ST, Xu XH, Zhu CM, Zhu QR. Epidemiological surveillance of norovirus and rotavirus diarrhea among outpatient children in five metropolitan cities. Zhonghua Er Ke Za Zhi 2010;48:564-70.

43. Chan-It W, Thongprachum A, Okitsu S, Nishimura S, Kiku-ta H, Baba T, et al. Detection and genetic characterization of norovirus infections in children with acute gastroenteritis in japan, 2007-2009. Clin Lab 2011;57:213-20.

44. Yu JH, Kim NY, Koh YJ, Lee HJ. Epidemiology of foodborne norovirus outbreak in Incheon, Korea, j Korean Med Sci 2010;25:1128-33.

45. Thongprachum A, Khamrin P, Chaimongkol N, Malasao R, Okitsu S, Mizuguchi M, et al. Evaluation of an immunoch-romatography method for rapid detection of noroviruses in clinical specimens in Thailand. j Med Virol 2010;82:2106-9.

46. Yanga SY, Hwanga KP, Wu FT, Wu HS, Hsiung CA, Chang WC, et al. Epidemiology and clinical peculiarities of norovirus and rotavirus infection in hospitalized young children with acute diarrhea in Taiwan. J Microbiol Immunol Infect 2010;43:506-14.

47. Bruggink L, Marshall J. The relationship between health care and nonhealth care norovirus outbreak settings and norovirus genotype in Victoria, Australia, 2002-2005. j Microbiol Immunol Infect 2011;44:241-6.

48. Mahar JE, Kirkwood CD. Characterization of norovirus strains in Australian children from 2006 to 2008: prevalence of recombinant strains, j Med Virol 2011;83:2213-9.

49. Uyar Y, Carhan A, Ozkaya E, Ertek M. Evaluation of laboratory diagnosis of the first Norovirus outbreak in Turkey in 2008. Mikrobiyol Bui 2008;42:607-15.

50. Altindis M, Banyai K, Kalaya R. Frequency of norovirus in stool samples from hospitalized children due to the acute gastroenteritis in Anatolia, Turkey, 2006-2007. Scand ] Infect Dis 2009;41:685-8.

51. Albayrak N, Yağcı Çağlayık D, Altaş AB, Korukluoğlu C, Ertek M. 2009 yılı akut viral gastroenterit verilerinin değerlendirilmesi. Turk Hi] Den Biyol Derg 2011;68:9-15.

52. Ozkul AA, Kocazeybek BS, Turan N, Reuter G, Bostan K, Yılmaz A, et al. Frequency and phytogeny of norovirus in dı-arrheic children in Istanbul, Turkey. J din Virol 2011;51:160-4.

Kaynak Göster