The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito

Abstract

Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence–but coming at the cost of optimal replication in humans–and may represent a first step towards a future emergence event.

Assessment of Mayaro virus vector competence of the mosquito Aedes aegypti (Linnaeus, 1762) populations in Argentine using dose–response assays

“…albopictus (Skuse, 1895) (Tsetsarkin et al, 2007). A recent study by Cereghino et al (2023) highlighted that the T179N mutation in the E2 protein increased Ae. aegypti vector competence for MAYV‐D but reduced pathogenicity and viraemia levels in mouse models.…”

Mayaro virus pathogenesis and immunity in rhesus macaques

“…MAYV is primarily transmitted by Haemagogus sp. mosquitos dwelling in tropical forests, but experimental studies have shown other species to be capable of transmission [8][9][10][11][12][13]. Transmission is maintained in sylvatic transmission cycles by non-human primate (NHP) primary hosts and by rodent or other secondary hosts [14].…”