Arboviral encephalitides: transmission, emergence, and pathogenesis

Abstract

Arthropod-borne viruses (arboviruses) are of paramount concern as a group of pathogens at the forefront of emerging and re-emerging diseases. Although some arboviral infections are asymptomatic or present with a mild influenza-like illness, many are important human and veterinary pathogens causing serious illness ranging from rash and arthritis to encephalitis and hemorrhagic fever. Here, we discuss arboviruses from diverse families (Flaviviruses, Alphaviruses, and the Bunyaviridae) that are causative agents of encephalitis in humans. An understanding of the natural history of these infections as well as shared mechanisms of neuroinvasion and neurovirulence is critical to control the spread of these viruses and for the development of effective vaccines and treatment modalities.

Fig. 1

Representative life cycles of arboviruses. Arboviruses are maintained in nature through an invertebrate reservoir cycle and a vertebrate amplification cycle. Mosquitoes are the representative vectors in this figure. However, other hematophagous invertebrates can serve as arboviral vectors. For many arboviruses, vertical transmission from an infected female mosquito to her progeny occurs via transovarial infection of eggs (e.g., LACV [red] and WNV [green]; Patrican and DeFoliart 1987; Watts et al. 1974; Young et al. 2008). Infected male mosquitoes can infect naïve female mosquitoes by venereal transmission. Upon taking a blood meal, infected mosquitoes may transmit virus to amplifying vertebrate hosts. These amplifying hosts develop brief, but high viremias that may lead to subsequent infection of other hematophagous mosquitoes from either the same or different mosquito species. In the enzootic cycle, arboviruses use sylvatic (red and green) transmission (e.g., LACV, small rodents and WNV and St. Louis encephalitis virus (SLEV), birds). In most cases, humans serve as dead-end hosts and do not play a major role in maintaining the arbovirus lifecycle. However, some arbovirus (e.g., VEEV, horses and JEV, pigs) have established epizootic amplification cycles in domestic animals (gray). Of increasing concern, some arboviruses (e.g., DENV) can rely on human amplification (blue) in an urban setting