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PeerJ. 2017 Apr 27;5:e3245. doi: 10.7717/peerj.3245. eCollection 2017.

On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles.

PeerJ

Carlos A M Carvalho, Jerson L Silva, Andréa C Oliveira, Andre M O Gomes

Affiliations

  1. Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  2. Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
  3. Current address: Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ministério da Saúde, Ananindeua, Pará, Brazil.

PMID: 28462045 PMCID: PMC5410162 DOI: 10.7717/peerj.3245

Abstract

Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell.

Keywords: Arboviruses; Caveolae-derived vesicles; Clathrin-coated vesicles; Endocytosis; Mayaro virus; Virus entry

Conflict of interest statement

Jerson L. Silva is an Academic Editor for PeerJ.

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