Mayaro virus disease

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Mayaro virus disease is a mosquitoborne zoonotic pathogen endemic to certain humid forests of tropical South America. Infection with Mayaro virus causes an acute, self-limited dengue-like illness of 3–5 days' duration.[1] The causative virus, abbreviated MAYV, is in the family Togaviridae, and genus Alphavirus. It is closely related to other alphaviruses that produce a dengue-like illness accompanied by long-lasting arthralgia. It is only known to circulate in tropical South America.[1]

Virology[edit]

Mayaro Virus has a structure similar to other Alphavirus. MAYV is an enveloped virus and has an icosahedral capsid with a diameter of 70 nm. The virus genome is composed of a linear, positive sense, single-stranded RNA with 11,429 nucleotides, excluding the 5’ cap nucleotide and 3’ poly(A) tail.[2][3]

The MAYV RNA genome contains the 5’ untranslated region (UTR), 3’ non-coding region (NCR) and two open reading frames (ORFs). The 5’ proximal and 3’ proximal ORFs are separated by a short non-coding sequence and represent two-third and one-third of the genomic RNA, respectively. The 5’-proximal ORF codes for a polyprotein that after cleavage forms non-structural proteins (nsP1, nsP2, nsP3, nsP4) and the 3’-proximal ORF with a 26S promoter codes for a polyprotein that is cleaved into structural proteins to generate capsid proteins and envelope surface glycoproteins (E1, E2, E3, C, 6K).[2][4][5][6]

The non-structural proteins (nsP) play different functions in the virus cycle. The non-structural protein 1 (nsP1) is an mRNA-capping enzyme, nsP2 has protease activity, nsP4 is a RNA-direct RNA polymerase. The structural polyprotein is cleaved into 6 chains: Capsid protein (C), p62, E3 protein or spike glycoprotein E3, E2 envelope glycoprotein or spike glycoprotein E2, 6K protein, E1 envelope glycoprotein known also as spike glycoprotein E1.[7][8] The envelope lipid component is critical for virus particle stability and infectivity in mammalian cells[9] Once the virus enters into the host cell, the genomic RNA is released into the cytoplasm, where the two ORFs are translated into proteins and the synthesis of negative-strand RNA starts. A consecutive synthesis of positive-strand RNA takes place.[8]

The MAYV sequences analysis showed two genotypes (D and L). The amplicon used for phylogenetic analysis includes E1 and E2 glycoprotein genes and the 3’ NCR. The genotype D is distributed in Trinidad, Brasil, French Guiana, Surinam, Peru and Bolivia while the genotype L is limited to the northcentral region of Brasil[10]

Diagnosis[edit]

The MAYV infection is characterized by fever, headache, myalgia, rash, prominent pain in the large joints, and association with rheumatic disease,[11][12] but these signs and symptoms are unspecific to distinguish from other Arbovirus. The MAYV infection can be confirmed by laboratory testing such us virus isolation, RT-PCR and serology. The virus isolation in cell culture is effective during viremia. RT-PCR helps to identify virus. Serology tests detect antibodies like IgM and the most common assay is IgM-capture enzyme-linked immunosorbant assays (ELISA). This test usually requires a consecutive retest to confirm increasing titers.[13][14] While the IgG detection is applied for epidemiology studies[15]

Epidemiology[edit]

The virus’s transmission cycle in the wild is similar to the continuous sylvatic cycle of yellow fever and is believed to involve wild primates (monkeys) as the reservoir and the tree-canopy-dwelling Haemagogus species mosquito as the vector.[1] Human infections are strongly associated with exposure to humid tropical forest environments. Chikungunya virus is closely related, producing a nearly indistinguishable, highly debilitating arthralgic disease. On February 19, 2011, a Portuguese-language news source reported on a recent survey which revealed Mayaro virus activity in Manaus, Amazonas State, Brazil.[16] The survey studied blood samples from 600 residents of Manaus who had experienced a high fever; Mayaro virus was identified in 33 cases. Four of the cases experienced mild hemorrhagic (bleeding) symptoms, which had not previously been described in Mayaro virus disease. The report stated that this outbreak is the first detected in a metropolitan setting, and expressed concern that the disease might be adapting to urban species of mosquito vectors, which would make it a risk for spreading within the country. A study published in October 2011 demonstrated that Aedes aegypti can transmit MAYV, supporting the possibility of wider transmission of Mayaro virus disease in an urban setting.[17]

Recent Cases[edit]

An outbreak in Chuquisaca Department, Bolivia, involving twelve persons, was reported in May 2007.[18]

In January 2010, a French tourist developed high-grade fever and severe joint pain manifestations following a 15 day trip in the Amazon basin, Brazil, and was diagnosed with MAYV infection in France. This case is the first reported in a traveler returning from an endemic South American country to Europe.[19] Mayaro virus disease has also been transported into the United States by two visitors infected in eastern Peru[20] and into the Netherlands by a couple infected while vacationing in Surinam.[21]

The first outbreak of Mayaro virus disease in humans in Venezuela was reported in early June 2010, with 69 cases diagnosed in Ospino, Portuguesa state, and an additional two in San Fernando de Apure, Apure state, on 7 June 2010, for a total of 71 reported cases as of 8 June.[22] A virologist noted that the symptoms induced by Mayaro virus in the New World are atypical in the New World, supporting the theory that Mayaro virus is an Old World virus that was introduced to the New World, possibly via the slave trade.[23]

Treatment[edit]

Recent research has suggested that macrophage migration inhibitory factor plays a critical role in determining the clinical severity of alphavirus-induced musculoskeletal disease and may provide a target for development of antiviral pharmaceuticals for Mayaro virus and other arthrogenic alphaviruses, such as Ross River virus, chikungunya, Sindbis virus, and O'nyong'nyong virus.[24]

References[edit]

  1. ^ a b c Receveur MC, Grandadam M, Pistone T, Malvy D. Infection with Mayaro virus in a French traveller returning from the Amazon region, Brazil, January, 2010. Euro Surveill. 2010;15(18):pii=19563. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19563.
  2. ^ a b Lavergne A, de Thoisy B, Lacoste V, Pascalis H, Pouliquen JF, Mercier V, Tolou H, Dussart P, Morvan J, Talarmin A, Kazanji M. “Mayaro virus: complete nucleotide sequence and phylogenetic relationships with other alphaviruses”. Virus Res. 2006 May;117(2):283-90. PMID 16343676. 
  3. ^ Mourão MP, Bastos Mde S, de Figueiredo RP, Gimaque JB, Galusso Edos S, Kramer VM, de Oliveira CM, Naveca FG, Figueiredo LT. “Mayaro fever in the city of Manaus, Brazil, 2007-2008”. Vector Borne Zoonotic Dis. 2012 Jan;12(1):42-6. PMID 21923266. 
  4. ^ Snyder AJ, Mukhopadhyay S. “The alphavirus E3 glycoprotein functions in a clade-specific manner”. J Virol. 2012 Dec;86(24):13609-20. PMID 23035234. 
  5. ^ Firth AE, Chung BY, Fleeton MN, Atkins JF. “Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma”. Virol J. 2008 Sep 26;5:108. PMID 18822126. 
  6. ^ Muñoz M., Navarro J.C. “Virus Mayaro: un arbovirus reemergente en Venezuela y Latinoamérica”. Biomédica vol.32 no.2 Bogotá Apr./June 2012"ISSN 0120-4157". 
  7. ^ Netto M.C.M.G., Shirako Y., Strauss E.G., Carvalho M.G.C., Strauss J.H. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases"Q8QZ73 (POLN_MAYAB)". 
  8. ^ a b Leung JY, Ng MM, Chu JJ. “Replication of alphaviruses: a review on the entry process of alphaviruses into cells”. Adv Virol. 2011;2011:249640. PMID 22312336. 
  9. ^ Sousa IP Jr, Carvalho CA, Ferreira DF, Weissmüller G, Rocha GM, Silva JL, Gomes AM. “Envelope lipid-packing as a critical factor for the biological activity and stability of alphavirus particles isolated from mammalian and mosquito cells”.J Biol Chem. 2011 Jan 21;286(3):1730-6. PMID 21075845. 
  10. ^ Powers A, Aguilar P, Chandler L, Brault A, Meakins T, Watts D, et al. Genetic relationships among Mayaro and Una viruses suggest distinct patterns of transmission. Am J Trop Med Hyg. 2006;75:461-9. PMID 16968922. 
  11. ^ Figueiredo LT. “Emergent arboviruses in Brazil”. Rev Soc Bras Med Trop. 2007 Mar-Apr;40(2):224-9. PMID 17568894. 
  12. ^ Suhrbier A, Jaffar-Bandjee MC, Gasque P. “Arthritogenic alphaviruses an overview”. Nat Rev Rheumatol. 2012 May 8;8(7):420-9. PMID 22565316. 
  13. ^ Forshey BM, Guevara C, Laguna-Torres VA, Cespedes M, Vargas J, Gianella A, Vallejo E, Madrid C, Aguayo N, Gotuzzo E, Suarez V, Morales AM, Beingolea L, Reyes N, Perez J, Negrete M, Rocha C, Morrison AC, Russell KL, Blair PJ, Olson JG, Kochel TJ; NMRCD Febrile Surveillance Working Group. “Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007”. PLoS Negl Trop Dis. 2010 Aug 10;4(8):e787. PMID 20706628. 
  14. ^ Wang E, Paessler S, Aguilar P, Carrara A, Ni H, Greene I, et al. Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections. J Clin Microbiol. 2006;44:4000-8. PMID 16957044. 
  15. ^ Abad-Franch F, Grimmer GH, de Paula VS, Figueiredo LT, Braga WS, Luz SL.”Mayaro virus infection in amazonia: a multimodel inference approach to risk factor assessment”. PLoS Negl Trop Dis. 2012;6(10):e1846. PMID 23071852. 
  16. ^ Redação NotíciasNX: "Manaus tem surto de vírus semelhante ao da dengue", http://www.noticiasnx.com.br/2010/index.php?option=com_content&view=article&id=25048:-manaus-tem-surto-de-virus-semelhante-ao-da-dengue-&catid=47:ultimas-noticias, Sábado, 19 de Fevereiro de 2011 09:39.
  17. ^ Long, Kanya C., Sarah A. Ziegler, Saravanan Thangamani, Nicole L. Hausser, Tadeusz J. Kochel, Stephen Higgs and Robert B. Tesh. 2011. Experimental Transmission of Mayaro Virus by Aedes aegypti. American Journal of Tropical Medicine and Hygiene 85(4): 750-757.
  18. ^ Agencia EFE: Seis regiones de Bolivia afectadas por brote de epidemias tras las lluvias, http://noticias.terra.com/noticias/articulo/html/act834981.htm, La Paz, 13 May 2007.
  19. ^ International Society for Infectious Diseases: PRO/AH/EDR> Mayaro virus disease - France ex Brazil, http://www.promedmail.org/pls/apex/f?p=2400:1001:4169803579523517::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82598, 07-MAY-2010.
  20. ^ R. B. Tesh, D. M. Watts, K. L. Russell, C. Damodaran, C. Calampa, C. Cabezas, G. Ramirez, B. Vasquez, C. G. Hayes, C. A. Rossi, A. M. Powers, C. L. Hice, L. J. Chandler, B. C. Cropp, N. Karabatsos, J. T. Roehrig, and D. J. Gubler. 1999. Mayaro virus disease: an emerging mosquito-borne zoonosis in tropical South America. Clinical Infectious Diseases 28(1): 67-73; http://www.ncbi.nlm.nih.gov/pubmed/10028074.
  21. ^ R. J. Hassing, I. Leparc-Goffart, S. N. Blank, S. Thevarayan, H. Tolou, G. van Doornum, and P. J. van Genderen. 2010. Imported Mayaro virus infection in the Netherlands. Journal of Infection 61(4): 343-345; http://www.ncbi.nlm.nih.gov/pubmed/20600300.
  22. ^ Giuliana Chiappe: “Detectan dos casos más de fiebre mayaro en Apure”, http://www.eluniversal.com/2010/06/06/pol_art_detectan-dos-casos-m_1928906.shtml, 00:19 GMT, 7 June 2010.
  23. ^ Professor E A Gould: “ProMED: Mayaro Virus Disease – Venezuela (02): Comment”, http://www.promedmail.org/pls/apex/f?p=2400:1001:2651078590147519::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,83114, June 07, 2010.
  24. ^ Herrero, L. J., Nelson, M., Srikiatkhachorn, A., Gu, R., Anantapreecha, S., Fingerle-Rowson, G., Bucala, R., Morand, E., Santos, L. L., Mahalingam, S. 2011. Critical role for macrophage migration inhibitory factor in Ross River virus-induced arthritis and myositis. Proceedings of the National Academy of Sciences USA, http://www.pnas.org/content/early/2011/06/29/1101089108.short?rss=1, published ahead of print July 5, 2011.