Mayaro Virus Pathogenesis and Transmission Mechanisms

Abstract

Mayaro virus (MAYV), isolated for the first time in Trinidad and Tobago, has captured the attention of public health authorities worldwide following recent outbreaks in the Americas. It has a propensity to be exported outside its original geographical range, because of the vast distribution of its vectors. Moreover, most of the world population is immunologically naïve with respect to infection with MAYV which makes this virus a true threat. The recent invasion of several countries by Aedesalbopictus underscores the risk of potential urban transmission of MAYV in both tropical and temperate regions. In humans, the clinical manifestations of MAYV disease range from mild fever, rash, and joint pain to arthralgia. In the absence of a licensed vaccine and clinically proven therapeutics against Mayaro fever, prevention focuses mainly on household mosquito control. However, as demonstrated for other arboviruses, mosquito control is rather inefficient for outbreak management and alternative approaches to contain the spread of MAYV are therefore necessary. Despite its strong epidemic potential, little is currently known about MAYV. This review addresses various aspects of MAYV, including its epidemiology, vector biology, mode of transmission, and clinical complications, as well as the latest developments in MAYV diagnosis.

Keywords: Aedes; Mayaro; Togaviridae; alphavirus; emerging arbovirus; vector competence.

Figure 1

Global distribution of Mayaro virus (MAYV). The virus was detected in vectors, non-human primates and humans. The first imported cases were reported in the United States in 1997 and in Europe in 2008. The origin of imported cases is shown in parentheses. These reports do not exclude the possible presence of MAYV in other countries, notably Africa and Asia. MAYV is not necessarily present throughout the countries/territories shaded in this map. ArcGIS Desktop V 10.5 software was used to generate this map (ESRI 2019, Redlands, CA, USA: Environmental Systems Research Institute; https://desktop.arcgis.com/en/).

Figure 2

Pathogenesis of Mayaro fever. Time course of MAYV viremia and detection of immunoglobulin M/G (IgM/IgG) after the inoculation of MAYV into a susceptible host by an infected mosquito. Duration of clinical manifestations that may appear in an infected individual. The figure was designed using Adobe Creative Cloud apps (https://www.adobe.com/creativecloud.html).

Figure 3

Diagram showing the probable dissemination of MAYV in humans, based on animal experiments and clinical data for similar alphaviruses. Transmission of MAYV occurs following its inoculation by an infected mosquito (Haemagogus janthinomys, Aedes aegypti, etc.). The virus then replicates in the skin (more precisely at the inoculation site of the virus by the competent vector) and propagates into the target tissues (muscle, the liver, joints, etc.) via the numerous blood vessels, followed by the recruitment of inflammatory cells in these tissues. Most of the target cells have not yet been identified for MAYV but the diagram shows an extrapolation based on other alphaviruses. The figure was designed using Adobe Creative Cloud apps (https://www.adobe.com/creativecloud.html).

Figure 4

The replicative cycle and genomic structure of MAYV. E: envelope; nsP: nonstructural protein; UTR: untranslated region; nt: nucleotides. A: nsP1 is required in the formation of the viral RNA and the RNA capping processing; B: nsP2 presents several enzymes required in transcription; C: nsP3 is one element of the replication complex; D: nsP4 is known as the viral RNA polymerase. 1: endocytosis through a clathrin-coated pit or, alternatively, through a caveolin-coated pit; 2: start of virus internalization with receptors of the host cell; 3: the low pH obtained in the endosome leads to structural modifications in the envelope of the virus that reveal the E1. The latter mediates cell membrane-virus fusion; 4: endosomal cell membrane-virus fusion; 5: release of the capsid core and genome of the virus; 6: from the mRNA of the virus, a pair of nsP precursors are generated; 7: the replication complex is obtained from the gathering of nsP proteins. This complex thus allows the synthesis of a minus-strand RNA; 8: this RNA is used as the model to generate both genomic (49S) and subgenomic (26S) RNAs; 9a: processing of the polyprotein precursor by an autoproteolytic serine protease; 9b: genomic RNA involved in nucleocapsid core assembly and genomic RNA packaging; 10: processing and maturation of glycoproteins pE2 and E1; 11: in the Golgi, processed glycoproteins are associated. Then they are transported into the cell membrane; 12a: at the cell membrane, the pE2 is split into E2 and E3; 12b: association of the viral RNA with the capsid C and the recruitment of E1 allows viral assembly; 13: particles of MAYV associated with the core are released outside of the host cell through the membrane. The figure was designed using Adobe Creative Cloud apps (https://www.adobe.com/creativecloud.html).

Figure 5

MAYV transmission cycles in endemic South and Central Americas. The list of arthropod and vertebrate species or groups mentioned in this figure may not be exhaustive due to the lack of data for certain regions. The figure was designed using Adobe Creative Cloud apps (https://www.adobe.com/creativecloud.html).

Figure 6

Worldwide distribution of Ae. albopictus and Ae. aegypti. The “tiger mosquito”, Ae. albopictus, has currently conquered several temperate regions including France, Italy, and Spain as shown on this map. The species is indeed a competent vector for several alphaviruses and flaviviruses which raises concerns when considering the occurrence of imported cases reported in the USA and Europe. On the other hand, Ae. aegypti is present in almost all tropical regions across the globe. On many occasions, the World Health Organization and the Rockefeller foundation have tried unsuccessfully to eradicate it. These two main urban vectors are not necessarily present throughout the countries/territories shaded in this map. ArcGIS Desktop V 10.5 software was used to generate this map (ESRI 2019, Redlands, CA, USA: Environmental Systems Research Institute; https://desktop.arcgis.com/en/).

Figure 7

Schematic diagram showing the ecological factors that affect MAYV transmission. The dashed line and double arrows illustrate possible interactions between factors. * Population-level susceptibility. The figure was designed using Adobe Creative Cloud apps (https://www.adobe.com/creativecloud.html).