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Arboviruses constitute a major public health problem; in particular mosquito-borne arboviruses that continuously emerge and re-emerge. Arbovirus infection of mammals is enhanced by the presence of a mosquito-bite at the inoculation site, or by the co-inoculation of extracted mosquito saliva alongside virus, in comparison to virus experimentally administered by needle inoculation in the absence of bite/saliva. Host responses elicited against saliva appear to be key in facilitating this enhancement. As such, we have studied the mechanistic basis for these observations by investigating mosquito-bite factors, as well as host responses, involved in facilitating viral enhancement. Using an in vivo mouse model we demonstrate that salivary microbiota does not modulate virus infection. Instead proteinaceous salivary factors inside saliva is responsible for enhancing virus infection. We have studied whether saliva from different mosquito species successfully enhance virus infection. Interestingly, while saliva from Aedes genus enhance virus infection, An.gambiae saliva does not. This could partly explain why An.gambiae mosquitos are unsuitable vectors for transmitting most arboviruses. By comparing the effects that saliva from these different species have at the inoculation-site, we have further specified which inflammatory responses modulate arbovirus infection in the skin. Using an in vivo mouse-model we demonstrate that An.gambiae causes significantly less oedema than Ae.aegypti and that histamine induced oedema in the absence of salivary-factors also enhances infection. Also, measuring cytokine responses to Aedes and Anopheles saliva, showed that several key anti-viral chemokines such as CCL5 were significantly more upregulated by Anopheles. Hence, we’re providing important insights into how mosquito saliva modulates infection. A better understanding of this will aid the development of anti-viral treatments targeting factors within the mosquito bite that are common to many distinct infections.