Mayaro virus disease

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

Mayaro virus
Virus classification
Group: Group IV ((+)ssRNA)
Order: Unassigned
Family: Togaviridae
Genus: Alphavirus
Species: Mayaro virus

Mayaro Virus has a structure similar to other Alphavirus. It 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

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

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 1991 demonstrated that a colonized strain of Brazilian Aedes albopictus was capable of acquiring MAYV from infected hamsters and subsequently transmitting it[17] and a study published in October 2011 demonstrated that Aedes aegypti can transmit MAYV, supporting the possibility of wider transmission of Mayaro virus disease in urban settings.[18]

Recent Cases

An outbreak in Chuquisaca Department, Bolivia, involving twelve persons, was reported in May 2007.[19]

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.[20] Mayaro virus disease has also been transported into the United States by two visitors infected in eastern Peru[21] and into the Netherlands by a couple infected while vacationing in Surinam.[22]

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.[23] 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.[20]

Treatment

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

  1. 1 2 3 Receveur MC, Grandadam M, Pistone T, Malvy D (2010). "Infection with Mayaro virus in a French traveller returning from the Amazon region, Brazil, January, 2010". Euro Surveillance 15 (18). PMID 20460093.
  2. 1 2 Lavergne A, de Thoisy B, Lacoste V, Pascalis H, Pouliquen JF, Mercier V, Tolou H, Dussart P, Morvan J, Talarmin A, Kazanji M (2006). "Mayaro virus: complete nucleotide sequence and phylogenetic relationships with other alphaviruses". Virus Research 117 (2): 283–90. doi:10.1016/j.virusres.2005.11.006. 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 (2012). "Mayaro fever in the city of Manaus, Brazil, 2007-2008". Vector Borne and Zoonotic Diseases 12 (1): 42–6. doi:10.1089/vbz.2011.0669. PMC 3249893. PMID 21923266.
  4. ↑ Snyder AJ, Mukhopadhyay S (2012). "The alphavirus E3 glycoprotein functions in a clade-specific manner". Journal of Virology 86 (24): 13609–20. doi:10.1128/JVI.01805-12. PMC 3503070. PMID 23035234.
  5. ↑ Firth AE, Chung BY, Fleeton MN, Atkins JF (2008). "Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma". Virology Journal 5: 108. doi:10.1186/1743-422X-5-108. PMC 2569925. PMID 18822126.
  6. ↑ Muñoz, Manuel; Navarro, Juan Carlos (2012). "Virus Mayaro: un arbovirus reemergente en Venezuela y Latinoamérica" [Mayaro virus: A re-emerging arboviruses in Venezuela and Latin America]. Biomédica 32 (2). doi:10.7705/biomedica.v32i2.647.
  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. 1 2 Leung JY, Ng MM, Chu JJ (2011). "Replication of alphaviruses: a review on the entry process of alphaviruses into cells". Advances in Virology 2011: 249640. doi:10.1155/2011/249640. PMC 3265296. PMID 22312336.
  9. ↑ Sousa IP, Carvalho CA, Ferreira DF, Weissmüller G, Rocha GM, Silva JL, Gomes AM (2011). "Envelope lipid-packing as a critical factor for the biological activity and stability of alphavirus particles isolated from mammalian and mosquito cells". The Journal of Biological Chemistry 286 (3): 1730–6. doi:10.1074/jbc.M110.198002. PMC 3023467. PMID 21075845.
  10. ↑ Powers AM, Aguilar PV, Chandler LJ, Brault AC, Meakins TA, Watts D, Russell KL, Olson J, Vasconcelos PF, Da Rosa AT, Weaver SC, Tesh RB (2006). "Genetic relationships among Mayaro and Una viruses suggest distinct patterns of transmission". The American Journal of Tropical Medicine and Hygiene 75 (3): 461–9. PMID 16968922.
  11. ↑ Figueiredo LT (2007). "Emergent arboviruses in Brazil". Revista Da Sociedade Brasileira De Medicina Tropical 40 (2): 224–9. doi:10.1590/S0037-86822007000200016. PMID 17568894.
  12. ↑ Suhrbier A, Jaffar-Bandjee MC, Gasque P (2012). "Arthritogenic alphaviruses--an overview". Nature Reviews. Rheumatology 8 (7): 420–9. doi:10.1038/nrrheum.2012.64. 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 (2010). "Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007". PLoS Neglected Tropical Diseases 4 (8): e787. doi:10.1371/journal.pntd.0000787. PMC 2919378. PMID 20706628.
  14. ↑ Wang E, Paessler S, Aguilar PV, Carrara AS, Ni H, Greene IP, Weaver SC (2006). "Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections". Journal of Clinical Microbiology 44 (11): 4000–8. doi:10.1128/JCM.00175-06. PMC 1698312. PMID 16957044.
  15. ↑ Abad-Franch F, Grimmer GH, de Paula VS, Figueiredo LT, Braga WS, Luz SL (2012). "Mayaro virus infection in amazonia: a multimodel inference approach to risk factor assessment". PLoS Neglected Tropical Diseases 6 (10): e1846. doi:10.1371/journal.pntd.0001846. PMC 3469468. PMID 23071852.
  16. ↑ "Manaus tem surto de vírus semelhante ao da dengue" [Manaus has virus outbreak similar to dengue]. Folha de S. Paulo. February 19, 2011.
  17. ↑ Smith GC, Francy DB (1991). "Laboratory studies of a Brazilian strain of Aedes albopictus as a potential vector of Mayaro and Oropouche viruses". Journal of the American Mosquito Control Association 7 (1): 89–93. PMID 1646286.
  18. ↑ 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.
  19. ↑ "Seis regiones de Bolivia afectadas por brote de epidemias tras las lluvias" [Six regions of Bolivia affected by outbreak of epidemics after rains]. Terra. May 13, 2007. Archived from the original on July 9, 2009.
  20. 1 2 Young, Alison (March 31, 2016). "Latest CDC lab incident involves worker infected with salmonella". USA Today.
  21. ↑ Tesh RB, Watts DM, Russell KL, Damodaran C, Calampa C, Cabezas C, Ramirez G, Vasquez B, Hayes CG, Rossi CA, Powers AM, Hice CL, Chandler LJ, Cropp BC, Karabatsos N, Roehrig JT, Gubler DJ (1999). "Mayaro virus disease: an emerging mosquito-borne zoonosis in tropical South America". Clinical Infectious Diseases 28 (1): 67–73. doi:10.1086/515070. PMID 10028074.
  22. ↑ Hassing RJ, Leparc-Goffart I, Blank SN, Thevarayan S, Tolou H, van Doornum G, van Genderen PJ (2010). "Imported Mayaro virus infection in the Netherlands". The Journal of Infection 61 (4): 343–5. doi:10.1016/j.jinf.2010.06.009. PMID 20600300.
  23. ↑ Chiappe, Giuliana (June 7, 2010). "Detectan dos casos más de fiebre mayaro en Apure" [Two more cases of Mayaro fever detected in Apure]. El Universal. Archived from the original on August 8, 2014.
  24. ↑ Herrero LJ, Nelson M, Srikiatkhachorn A, Gu R, Anantapreecha S, Fingerle-Rowson G, Bucala R, Morand E, Santos LL, Mahalingam S (2011). "Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis". Proceedings of the National Academy of Sciences of the United States of America 108 (29): 12048–53. doi:10.1073/pnas.1101089108. JSTOR 27978946. PMC 3141998. PMID 21730129.
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