Everglades virus evolution: Genome sequence analysis of the envelope 1 protein reveals recent mutation and divergence in South Florida wetlands

Abstract

Everglades virus (EVEV) is a subtype (II) of Venezuelan equine encephalitis virus (VEEV), endemic in southern Florida, USA. EVEV has caused clinical encephalitis in humans, and antibodies have been found in a variety of wild and domesticated mammals. Over 29,000 Culex. cedecei females, the main vector of EVEV, were collected in 2017 from Big Cypress and Fakahatchee Strand Preserves in Florida, and pool-screened for the presence of EVEV using reverse transcription real-time polymerase chain reaction. The entire E1 protein gene was successfully sequenced from 15 positive pools. Phylogenetic analysis showed that isolates clustered, based on location of sampling, into two monophyletic clades that diverged in 2009. Structural analyses revealed two mutations of interest, A116V and H441R, shared amongst all isolates obtained after its first isolation of EVEV in 1963, possibly reflecting adaptation to a new host. Alterations of the Everglades ecosystem may have contributed to the evolution of EVEV and its geographic compartmentalization. This is the first report that shows in detail the evolution of Everglades virus in South Florida. This zoonotic pathogen warrants inclusion into routine surveillance given the high natural infection rate in the vectors. Invasive species, increasing urbanization, the Everglades restoration, and modifications to the ecosystem due to climate change and habitat fragmentation in South Florida may increase rates of EVEV spillover to the human population.

Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA

“…The most comprehensive phylogenetic analysis to date for EVEV, based on sequences of the E1 gene of 17 isolates, including 16 from Culex cedecei Stone and Hair in 2017, revealed two main clades defined by location within the Everglades region, Big Cypress National Preserve (BCNP) and Fakahatchee State Park Preserve (Fig. 1), which diverged about 2009 (Valente et al 2022). Two substitutions, A116V and H441R, were shared among all 2017 isolates, possibly reflecting adaptation to a new host after 1963 based on the mutational history of other alphaviruses such as chikungunya.…”