Starvation at the larval stage increases the vector competence of Aedes aegypti females for Zika virus

Abstract

Aedes aegypti is the primary vector of Zika virus (ZIKV), a flavivirus which typically presents itself as febrile-like symptoms in humans but can also cause neurological and pregnancy complications. The transmission cycle of mosquito-borne arboviruses such as ZIKV requires that various key tissues in the female mosquito including the salivary glands get productively infected with the virus before the mosquito can transmit the virus to another vertebrate host. Following ingestion of a viremic blood-meal from a vertebrate, ZIKV initially infects the midgut epithelium before exiting the midgut after blood-meal digestion to disseminate to secondary tissues including the salivary glands. Here we investigated whether smaller Ae. aegypti females resulting from food deprivation as larvae exhibited an altered vector competence for blood-meal acquired ZIKV relative to larger mosquitoes. Midguts from small ‘Starve’ and large ‘Control’ Ae. aegypti were dissected to visualize by transmission electron microscopy (TEM) the midgut basal lamina (BL) as physical evidence for the midgut escape barrier showing Starve mosquitoes with a significantly thinner midgut BL than Control mosquitoes at two timepoints. ZIKV replication was inhibited in Starve mosquitoes following intrathoracic injection of virus, however, Starve mosquitoes exhibited a significantly higher midgut escape and population dissemination rate at 9 days post-infection (dpi) via blood-meal, with more virus present in saliva and head tissue than Control by 10 dpi and 14 dpi, respectively. These results indicate that Ae. aegypti developing under stressful conditions potentially exhibit higher midgut infection and dissemination rates for ZIKV as adults, Thus, variation in food intake as larvae is potentially a source for variable vector competence levels of the emerged adults for the virus.

Native Wolbachia infection and larval competition stress shape fitness and West Nile virus infection in Culex quinquefasciatus mosquitoes

“…Similarly, Ae. aegypti mosquitoes that experienced competition stress had a thinner midgut basal lamina and exhibited increased susceptibility to ZIKV infection ( Herd et al, 2021 ). However, these interactions can vary depending on the host-pathogen combination.…”

The influence of the larval microbiome on susceptibility to Zika virus is mosquito genotype dependent

“…The nutrition status and larval microbiome have previously been shown to influence mosquito fitness [41,42] and susceptibility to arboviruses [37,38,43,44]. The microbiome is composed of diverse microorganisms that colonize the mosquito's gut, interacting with the host's metabolic processes [38,45,46] and modulating its immune response [36,[47][48][49].…”

A cell atlas of the larval Aedes aegypti ventral nerve cord

“…For example, larvae exhibit well-developed optic lobes that resemble adult structures, and identified serotonergic neurons persist into adults [ 55 , 57 ]. Third, events in larval development including diet, thermal cues, intraspecies competition, and other environmental conditions directly impact pathogen infection and vectorial capacity of adults [ 2 , 18 , 25 , 41 , 56 ]. Finally, targeting larvae for population control provides potential advantages including the organism’s limited range and opportunities to intervene prior to reproductive maturity.…”