Host range amplification and arboviral disease emergence

Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, U.S.A.

Summary. Etiologic agents of arboviral diseases are primarily zoonotic pathogens that are maintained in nature in cycles involving arthropod transmission among a variety of susceptible reservoir hosts. In the simplest form of human exposure, spillover occurs from the enzootic cycle when humans enter zoonotic foci and/or enzootic amplification increases circulation near humans. Examples include Eastern (EEEV) and Western equine encephalitis viruses (WEEV), as well as West Nile (WNV), St. Louis encephalitis (SLEV) and Yellow fever viruses. Spillover can involve direct transmission to humans by primary enzootic vectors (e.g. WNV, SLEV and WEEV) and/or bridge vectors with more catholic feeding preferences that include humans (e.g. EEEV). Some viruses, such as Rift Valley fever, Japanese encephalitis and Venezuelan equine encephalitis viruses (VEEV) undergo secondary amplification involving replication in livestock animals, resulting in greater levels of spillover to humans in rural settings. In the case of VEEV, secondary amplification involves equines and requires adaptive mutations in en-zootic strains that allow for efficient viremia production. Two of the most important human arboviral pathogens, Yellow fever and dengue viruses (DENV), have gone one step further and adopted humans as their amplification hosts, allowing for urban disease. The ancestral forms of DENV, sylvatic viruses transmitted among nonhuman primate reservoir hosts by arboreal mosquitoes, adapted to efficiently infect the urban mosquito vectors Aedes aegypti and Ae. albopictus during the past few thousand years as civilizations arose. Comparative studies of the sylvatic and urban forms of DENV may elucidate the evolution of arboviral virulence and the prospects for DENV eradication should effective vaccines be implemented.

Arthropod-borne viruses, or arboviruses, include many zoonotic pathogens that are transmitted among vertebrate reservoir hosts by mosquitoes, ticks or other biting arthropods [6]. Arboviruses also include important human pathogens that cause a variety of serious and sometimes fatal diseases, particularly in the tropics. To infect humans, these viruses use a variety of mechanisms ranging from simple spillover from enzootic cycles to adaptations that alter their host ranges to include domestic animals, and enhance their amplification in proximity to humans

Sylvatic Cycle Arbovirus

Fig. 1. Cartoon showing mechanisms of human infection by zoonotic arboviruses. At the center is an enzootic cycle, typically involving avian, rodent or nonhuman primates as amplification and/or reservoir hosts and mosquito vectors. Humans become infected via direct spillover when they enter enzootic habitats and/or when amplification results in high levels of circulation. Transmission to humans may involve the enzootic vector or bridge vectors with broader host preferences. At right, secondary amplification involving domestic animals can increase circulation around humans, increasing their chance of infection via spillover. In the case of VEEV, mutations that enhance equine viremia are needed for secondary equine amplification. At left, dengue and Yellow fever viruses can use humans directly for amplification, resulting in urban epidemic cycles and massive outbreaks. In the case of dengue viruses, humans also serve as reservoir hosts

Fig. 1. Cartoon showing mechanisms of human infection by zoonotic arboviruses. At the center is an enzootic cycle, typically involving avian, rodent or nonhuman primates as amplification and/or reservoir hosts and mosquito vectors. Humans become infected via direct spillover when they enter enzootic habitats and/or when amplification results in high levels of circulation. Transmission to humans may involve the enzootic vector or bridge vectors with broader host preferences. At right, secondary amplification involving domestic animals can increase circulation around humans, increasing their chance of infection via spillover. In the case of VEEV, mutations that enhance equine viremia are needed for secondary equine amplification. At left, dengue and Yellow fever viruses can use humans directly for amplification, resulting in urban epidemic cycles and massive outbreaks. In the case of dengue viruses, humans also serve as reservoir hosts

(Fig. 1). In the most extreme example, dengue viruses (DENV-1-4, 4 different viruses) have evolved independently to adopt humans as their amplification and reservoir hosts, resulting in the emergence of tropical and subtropical pandemic disease during the past half century [10, 28]. This review describes examples of mechanisms of arboviral disease emergence and the effect of host range on human exposure and infection, with a focus on mosquito-borne viruses of the New World. Examples are largely drawn from the alphaviruses (Togaviridae: Alphavirus) [30] and flaviviruses (Flaviviridae: Flavivirus) [8], which, along with the bunyaviruses (Bunyaviridae) comprise the major taxa of arboviruses [6].

Direct arboviral spillover

Most mosquito-borne arboviruses utilize small mammalian or avian reservoir hosts (those responsible for long-term maintenance), which along with the vectors determine the distribution of transmission under normal circumstances (Fig. 1).

Bridge vectors e.g. Aedes, Coquillettidia

Arbovirus Influenza

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