Wednesday, August 28, 2024

Protein in mosquito saliva helps viruses spread to humans

Amazing stuff! What is in your saliva?

Why don't we eradicate blood suckers?

"... a protein called Nest1 found in the saliva of Aedes aegypti mosquitos ...

For the new study, researchers set out to better understand how Nest1 affects viral infection in humans.

First, the researchers exposed human skin explants — samples of human tissue donated for research — to Zika virus with and without Nest1. They found that Zika virus replicated significantly more quickly in human skin when combined with Nest1.

That finding suggested Nest1 was interacting with biological molecules in human skin. To identify which, the researchers tested Nest1 against more than 2,600 human proteins, looking to see if Nest1 attached to any of them. They found that Nest1 bound strongly to a molecule called Cluster of Differentiation 47, or CD47, which is involved in a number of immune processes. In fact, Nest1 bound 26-times more strongly to CD47 than did the human protein that naturally binds to it, ..."

From the editor's summary and abstract:
"Editor’s summary
Aedes aegypti mosquitos can transmit arboviruses during blood feeding, and components of mosquito saliva may enhance both blood feeding and virus transmission. ... identified a 34-kDa mosquito salivary protein called Nest1, highly expressed in the saliva of female A. aegypti mosquitos, as a high-affinity binder to human CD47. In human skin explants infected with Zika virus, Nest1 increased virus burden and inhibited some CD47-governed immune functions like phagocytosis and proinflammatory responses in immune cells, thus inhibiting antiviral responses. These findings provide insight into how mosquito salivary proteins can potentially facilitate arbovirus infection. ...
Abstract
The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity."

Protein in mosquito saliva helps viruses spread to humans | YaleNews

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