Tissue Barriers to Arbovirus Infection in Mosquitoes

Abstract

Arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. Arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. Following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. Once the vector has become systemically and persistently infected, the vector is able to transmit the virus to an uninfected vertebrate host. In order to systemically infect the vector, the virus must cope with innate immune responses and overcome several tissue barriers associated with the midgut and the salivary glands. In this review we describe, in detail, the typical arbovirus infection route in competent mosquito vectors. Based on what is known from the literature, we explain the nature of the tissue barriers that arboviruses are confronted with in a mosquito vector and how arboviruses might surmount these barriers. We also point out controversial findings to highlight particular areas that are not well understood and require further research efforts.

Rift Valley fever virus: strategies for maintenance, survival and vertical transmission in mosquitoes

“…2). The micro-organism, taken up in a blood meal, must cross or infect the gut epithelium, replicate, migrate to the salivary glands and be transmitted upon blood feeding [67,68]. Vectorial capacity depends on environmental and behavioural traits such as vector density, lifespan, biting rate, flight distance and host feeding preferences [69].…”

“…In a competent host, arboviruses are thought to infect midgut epithelial cells by host cell-mediated endocytosis, observed for some flaviviruses, alphaviruses and orthobunyaviruses (reviewed in [67]). Virus replicates within these cells, exiting into the haemocoel, commonly simplified into a single measure of dissemination.…”

“…Inability to enter or replicate in the midgut epithelium is termed the midgut infection barrier. Delay or prevention of dissemination is collectively termed the midgut escape barrier and is dose-dependent [71][72][73] interference (RNAi) (reviewed in [75]), virus inactivation by digestive enzymes and virus incompatibility with host receptors, for example deleting NSm in RVFV impedes infection in Aedes aegypti [67,76,77]. Once in the haemocoel, virus is actively circulated in the haemolymph to all tissues including the salivary glands and ovaries.…”

Primary Cell Culture of Aedes Albopictus Midgut Cells: A Prospective Model for in Vitro Study of Arboviruses

“…Due to unavailability of proper representation system which may imitate the host pathogen interactions, universally accepted vaccine and drug regimens are still unavailable to combat these lifethreatening diseases. In arboviral diseases such as dengue, Zika, West Nile, and yellow fever virus, the virus conduction from infected humans to mosquitoes occurs through an infectious blood meal and the midgut cell membrane is the portal of entry as well as the first cellular barrier where the virus interacts to establish infection [4]. The virus penetrates into the midgut epithelium, replicate, crosses the escape barrier, and disseminates into the salivary gland of the infected mosquitoes, from where the virus is transmitted to a new vertebrate host [4].…”

“…In arboviral diseases such as dengue, Zika, West Nile, and yellow fever virus, the virus conduction from infected humans to mosquitoes occurs through an infectious blood meal and the midgut cell membrane is the portal of entry as well as the first cellular barrier where the virus interacts to establish infection [4]. The virus penetrates into the midgut epithelium, replicate, crosses the escape barrier, and disseminates into the salivary gland of the infected mosquitoes, from where the virus is transmitted to a new vertebrate host [4]. Therefore, it is important to have a clear understanding of the vector-virus interactions, which may enable predictions of how these viruses can establish infections, disseminate from one organ to another and ultimately be applied to the development of more efficient disease control strategies.…”