Apoptosis in mosquito salivary glands: Sindbis virus-associated and tissue homeostasis

Abstract

Apoptosis is observed during a spectrum of conditions including exogenous virus infection and endogenous cellular turnover. Adult female Aedes albopictus mosquitoes challenged with increasing titres of Sindbis virus (SINV) via intrathoracic inoculation demonstrated that the injection dosage did not result in significantly different levels of virus growth or mosquito survival at day 10 post-infection. Tissues probed for apoptosis using an in situ TUNEL assay revealed SINV-associated apoptotic cells scattered throughout the proximal and distal regions of the salivary gland (SG) lateral lobes but which were not detected in the median lobe or the midgut and hindgut. Apoptosis was also identified in SG duct cells in both infected and uninfected mosquitoes, suggesting routine tissue homeostasis. SINV-associated apoptosis sequestered to the SG lateral lobes indicates a differential epithelial cell response to an arbovirus and provides insight into mosquito defence mechanisms against pathogens and SG infection barriers, hurdles to transmission of arboviruses of public health concern.

Rapid selection against arbovirus-induced apoptosis during infection of a mosquito vector

“…Lowering the amount of virus in saliva may decrease virus transmission, although the magnitude of the decrease probably depends on the virus and its ability to infect the host. A recent report found increased apoptosis in SINV-infected salivary glands in A. aegypti compared with uninfected glands (37). This and other studies reporting apoptosis in arbovirus-infected salivary glands (29,30) lend to the notion that apoptosis in salivary glands may naturally occur in some arbovirus-mosquito combinations and could explain why we observed decreased infection prevalence in saliva at 14 dpi compared with 10 dpi with all of the viruses tested.…”

“…SINV and A. aegypti have been used extensively as a model to study virus-vector interactions (34)(35)(36)(37)(38). SINV is well characterized molecularly and has been developed as an alphavirus transducing system in which a cDNA clone of the viral genome is engineered to allow expression of foreign genes during virus replication (36,39,40).…”

Apoptosis-related genes control autophagy and influence DENV-2 infection in the mosquito vector, Aedes aegypti

“…Our previous whole transcriptome study indicated that a group of genes associated with apoptosis showed significant coordinated upregulation in a DENV refractory strain in response to DENV-2 infection (Behura et al , 2011). Apoptosis of mosquito salivary gland and midgut tissue has been associated with infection by multiple viruses including, West Nile virus, Sindbis virus (SINV), densovirus and nucleopolyhedrovirus (Kelly et al , 2012; Liu et al , 2011; Roekring & Smith, 2010; Vaidyanathan & Scott, 2006). Progressive salivary gland apoptosis has been correlated with decreased long-term West Nile virus titers in Culex quinquefasciatus (Girard et al , 2007).…”

Arboviruses and apoptosis: the role of cell death in determining vector competence

“…Whether this pathological effect benefits the virus by allowing more rapid access to the haemocoel, or conversely helps to control virus replication, is not clear. There have also been reports of apoptosis in salivary glands of Aedes albopictus infected with Sindbis virus (SINV) (Bowers et al, 2003;Kelly et al, 2012) and Culex pipiens quinquefasciatus infected with WNV (Girard et al, 2005), leading the authors to postulate that cell death in salivary glands could be a mechanism that decreases feeding behaviour and/or leads to decreased virus release in saliva; this hypothesis was supported by the observation that, while apoptosis increased over time, the proportion of WNV-infected mosquitoes able to transmit virus decreased (Girard et al, 2007). In another case, apoptosis was observed in the midguts of a refractory laboratory strain of Culex pipiens pipiens infected with WNV but not in uninfected midguts.…”