Abstract:BackgroundDengue fever, caused by the dengue virus (DENV), is now the most common arbovirus transmitted disease globally. One novel approach to control DENV is to use the endosymbiotic bacterium, Wolbachia pipientis, to limit DENV replication inside the primary mosquito vector, Aedes aegypti. Wolbachia that is naturally present in a range of insects reduces the capacity for viruses, bacteria, parasites and fungi to replicate inside insects. Wolbachia’s mode of action is not well understood but may involve comp… Show more
“…aegypti populations. This sharply contrasts previous studies where Wolbachia infection significantly reduced the proportion of individuals infected with other flaviviruses such as DENV (Amuzu & McGraw, 2016; Amuzu, Simmons, & McGraw, 2015; Bian et al., 2013; Frentiu et al., 2014; Moreira et al., 2009; Walker et al., 2011), Zika (Aliota et al., 2016; Dutra et al., 2016), and YFV (van den Hurk et al., 2012). Our findings are, however, supported by studies performed in Cx.…”
Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect‐specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness. Wolbachia is an endosymbiotic bacterium of insects that when present in mosquitoes limits the replication of co‐infecting pathogens, including flaviviruses. Artificially created Wolbachia‐infected Aedes aegypti mosquitoes are being released into the wild in a series of trials around the globe with the hope of interrupting dengue and Zika virus transmission from mosquitoes to humans. Our work investigated the effect of Wolbachia on ISF infection in wild‐caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia‐infected mosquitoes compared to the Wolbachia‐free mosquitoes. Our findings demonstrate that the symbiont is capable of manipulating the mosquito virome and that Wolbachia‐mediated viral inhibition is not universal for flaviviruses. This may have implications for the Wolbachia‐based DENV control strategy if ISFs confer fitness effects or alter mosquito susceptibility to other flaviviruses.
“…aegypti populations. This sharply contrasts previous studies where Wolbachia infection significantly reduced the proportion of individuals infected with other flaviviruses such as DENV (Amuzu & McGraw, 2016; Amuzu, Simmons, & McGraw, 2015; Bian et al., 2013; Frentiu et al., 2014; Moreira et al., 2009; Walker et al., 2011), Zika (Aliota et al., 2016; Dutra et al., 2016), and YFV (van den Hurk et al., 2012). Our findings are, however, supported by studies performed in Cx.…”
Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect‐specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness. Wolbachia is an endosymbiotic bacterium of insects that when present in mosquitoes limits the replication of co‐infecting pathogens, including flaviviruses. Artificially created Wolbachia‐infected Aedes aegypti mosquitoes are being released into the wild in a series of trials around the globe with the hope of interrupting dengue and Zika virus transmission from mosquitoes to humans. Our work investigated the effect of Wolbachia on ISF infection in wild‐caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia‐infected mosquitoes compared to the Wolbachia‐free mosquitoes. Our findings demonstrate that the symbiont is capable of manipulating the mosquito virome and that Wolbachia‐mediated viral inhibition is not universal for flaviviruses. This may have implications for the Wolbachia‐based DENV control strategy if ISFs confer fitness effects or alter mosquito susceptibility to other flaviviruses.
“…In ovaries dissected from -Wolb and +Wolb mosquitoes that were orally challenged with DENV-4, we observed 71.29% decrease in prevalence of infection associated with w Mel (Fig. 1, Fisher’s exact test: P = 0.0002, OR = 0.0875, CI = 0.0237–0.327), which could indicate that the anti-DENV effect of Wolbachia can operate on the tissue level, or that the general inhibitory effect of Wolbachia limits the amount of virus that reaches the ovaries [21]. Critically, this effect disappeared after challenge with DENV-1 or DENV-4 via injection (Fisher’s exact test: DENV-1: P = 1, OR = 0.3171, CI = 0.0122–8.267; DENV-4: P = 0.4878, OR = 5.513, CI = 0.2488–122.2), highlighting the importance of the midgut to the anti-DENV effects of w Mel.Fig.…”
Background
Wolbachia pipientis is a common endosymbiotic bacterium of arthropods that strongly inhibits dengue virus (DENV) infection and transmission in the primary vector, the mosquito Aedes aegypti. For that reason, Wolbachia-infected Ae. aegypti are currently being released into the field as part of a novel strategy to reduce DENV transmission. However, there is evidence that DENV can be transmitted vertically from mother to progeny, and this may help the virus persist in nature in the absence of regular human transmission. The effect of Wolbachia infection on this process had not previously been examined.ResultsWe challenged Ae. aegypti with different Brazilian DENV isolates either by oral feeding or intrathoracic injection to ensure disseminated infection. We examined the effect of Wolbachia infection on the prevalence of DENV infection, and viral load in the ovaries. For orally infected mosquitoes, Wolbachia decreased the prevalence of infection by 71.29%, but there was no such effect when the virus was injected. Interestingly, regardless of the method of infection, Wolbachia infection strongly reduced DENV load in the ovaries. We then looked at the effect of Wolbachia on vertical transmission, where we observed only very low rates of vertical transmission. There was a trend towards lower rates in the presence of Wolbachia, with overall maximum likelihood estimate of infection rates of 5.04 per 1000 larvae for mosquitoes without Wolbachia, and 1.93 per 1000 larvae for Wolbachia-infected mosquitoes, after DENV injection. However, this effect was not statistically significant.ConclusionsOur data support the idea that vertical transmission of DENV is rare in nature, even in the absence of Wolbachia. Indeed, we observed that vertical transmission rates were low even when the midgut barrier was bypassed, which might help to explain why we only observed a trend towards lower vertical transmission rates in the presence of Wolbachia. Nevertheless, the low prevalence of disseminated DENV infection and lower DENV load in the ovaries supports the hypothesis that the presence of Wolbachia in Ae. aegypti would have an effect on the vertical transmission of DENV in the field.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2236-z) contains supplementary material, which is available to authorized users.
“…Nonetheless, this hypothesis should be further validated, given that we did not explicitly measure Wolbachia titers in the same flies that were used for our experiments. We highlight the importance of future experiments directly exploring the association between distinct bacterial strains, their intrinsic replicative ability, and the transcriptional level of sirt-4 , focusing on individuals of the same age, sex and host tissue, as Wolbachia density has been shown to affected by these factors [ 59 , 60 ].…”
Wolbachia
is an intracellular bacterial symbiont of arthropods notorious for inducing many reproductive manipulations that foster its dissemination.
Wolbachia
affects many aspects of host biology, including metabolism, longevity and physiology, being described as a nutrient provisioning or metabolic parasite, depending on the host-microbe association. Sirtuins (SIRTs) are a family of NAD
+
-dependent post-translational regulatory enzymes known to affect many of the same processes altered by
Wolbachia
, including aging and metabolism, among others. Despite a clear overlap in control of host-derived pathways and physiology, no work has demonstrated a link between these two regulators. We used genetically tractable
Drosophila melanogaster
to explore the role of sirtuins in shaping signaling pathways in the context of a host-symbiont model. By using transcriptional profiling and metabolic assays in the context of genetic knockouts/over-expressions, we examined the effect of several
Wolbachia
strains on host
sirtuin
expression across distinct tissues and timepoints. We also quantified the downstream effects of the
sirtuin
x
Wolbachia
interaction on host glucose metabolism, and in turn, how it impacted
Wolbachia
titer. Our results indicate that the presence of
Wolbachia
is associated with (1) reduced
sirt-4
expression in a strain-specific manner, and (2) alterations in host glutamate dehydrogenase expression and ATP levels, key components of glucose metabolism. We detected high glucose levels in
Wolbachia-
infected flies, which further increased when
sirt-4
was over-expressed. However, under
sirt-4
knockout, flies displayed a hypoglycemic state not rescued to normal levels in the presence of
Wolbachia
. Finally, whole body
sirt-4
over-expression resulted in reduced
Wolbachia
ovarian titer. Our results expand knowledge of
Wolbachia
-host associations in the context of a yet unexplored class of host post-translational regulatory enzymes with implications for conserved host signaling pathways and bacterial titer, factors known to impact host biology and the symbiont’s ability to spread through populations.
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