Alphaviruses: population genetics and determinants of emergence

Abstract

Alphaviruses are responsible for several medically important emerging diseases and are also significant veterinary pathogens. Due to the aerosol infectivity of some alphaviruses and their ability to cause severe, sometimes fatal neurologic diseases, they are also of biodefense importance. This review discusses the ecology, epidemiology and molecular virology of the alphaviruses, then focuses on three of the most important members of the genus: Venezuelan and eastern equine encephalitis and chikungunya viruses, with emphasis on their genetics and emergence mechanisms, and how current knowledge as well as gaps influence our ability to detect and determine the source of both natural outbreaks and potential use for bioterrorism. This article is one of a series in Antiviral Research on the genetic diversity of emerging viruses.

Fig. 1

Phylogenetic tree of the alphaviruses produced using Bayesian methods and mid-point rooted. Vectors and vertebrate hosts are printed next to virus labels. The tree include representatives from all species and was constructed using the structural protein E2, 6 K and E1 genes. The dashed line indicates the point at which ancestral SINV and EEEV recombined to form the recombinant WEEV ancestor. All posterior probabilities were 1 unless shown. Nodes with a ❖ symbol had posterior probabilities less than 0.9 and nodes with a ★ had no posterior support.

Fig. 2

Structure of the alphavirus virion. Left. Cryoelectron electron microscopic reconstruction of the VEEV strain TC-83 virion. Center. Cross section of the TC-83 virion showing the locations of the capsid proteins, and the plasma membrane-derived lipid envelope. Right. Enlargement of the envelope glycoprotein spikes, the transmembrane domains, and the interaction of the cytoplasmic tail of the E2 proteins with the capsid proteins. The figure was adapted from (Zhang et al., 2011) with permission.

Fig. 3

Genome organization of the alphaviruses with major protein functions listed below.

Fig. 4

Transmission cycles of VEEV including the enzootic cycle above and the epizootic/epidemic cycle below.

Fig. 5

Distribution of VEE complex alphaviruses in the Americas. Adapted from (Weaver and Reisen, 2009) with permission.

Fig. 6

Distribution of EEEV strains in the Americas including subtypes I–IV.

Fig. 7

Phylogenetic tree showing EEEV strains representing subtypes I–IV constructed using Bayesian methods, with the complete structural polyprotein open reading frames. Adapted from (Arrigo et al., 2010b) with permission.

Fig. 8

Transmission cycle of EEEV in North America, including dead end human and domesticated animal hosts that develop severe disease.

Fig. 9

Geographic distribution and history of CHIKV emergence, including strains from the Indian Ocean basin outbreak that began in 2004, exported cases in human travelers, and limited outbreaks in Europe. Adapted from (Weaver and Reisen, 2009) with permission.

Fig. 10

Phylogenetic tree of CHIKV strains derived from genomic sequences using Bayesian methods. The numbers adjacent to nodes indicate Bayesian posterior probability values. Strains colored Magenta contain the E1-226 V residue shown to enhance infection of the mosquito vector, A. albopictus.

Fig. 11

CHIKV transmission cycles including the enzootic cycle known only in Africa and the epidemic/endemic cycles that occur in Africa, Asia and on a temporary basis in Europe. Adapted from (Tsetsarkin et al., 2011b) with permission.