Dunlap Daugaard (burstarcher73)

Vector-borne diseases are responsible for over a billion infections each year and nearly one million deaths. Mosquito-borne dengue virus, West Nile, Japanese encephalitis, Zika, Chikungunya, and Rift Valley Fever viruses constitute major public health problems in regions with high densities of arthropod vectors. During the initial step of the transmission cycle, vector, host, and virus converge at the bite site, where local immune cells interact with the vector's saliva. Hematophagous mosquito saliva is a mixture of bioactive components known to modulate vertebrate hemostasis, immunity, and inflammation during the insect's feeding process. The capacity of mosquito saliva to modulate the host immune response has been well-studied over the last few decades and has led to the consensus that the presence of saliva is linked to the enhancement of virus transmission, host susceptibility, disease progression, viremia levels, and mortality. We review some of the major aspects of the interactions between mosquito saliva and the host immune response that may be useful for future studies on the control of arboviruses.Visceral leishmaniasis is a neglected tropical disease caused by Leishmania (L.) donovani parasite in the Indian subcontinent. Macrophages (mϕ) are the harboring cells for parasite and their interactions dictate the pathogenesis of this disease. Polyunsaturated fatty acids are an integral part of the mϕ cell membrane and are derived from linoleic acid (LA), which is a principal essential fatty acid. Here, we have investigated the effect of the simultaneous presence of LA during L. donovani infection in mϕ. Treatment with LA suppresses the parasitic load in mϕ (kDNA expression) and promotes the Th-1 type immune response (IL-12, iNOS). However, no significant change in kDNA expressions was observed when L. donovani promastigotes were treated with LA. Intrigued by this observation, we explored mechanism(s) by which LA promoted the protective type immune response in infected mϕ. Interestingly, LA decreased the release of L. donovani derived extracellular vesicle later characterized as microvesicles. Moreover, these microvesicles were suppressive concerning their bias toward the Th-2 type of immune responses (IL-10, Arginase) in mϕ. We suggest that LA plays a protective role in the immune response against L. donovani infection by inhibiting the release to Leishmania derived microvesicles and thus promoting Th-1 type immune response in mϕ.The spread of the novel coronavirus (SARS-CoV-2) has triggered a global emergency, that demands urgent solutions for detection and therapy to prevent escalating health, social, and economic impacts. The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells. The S proteins from SARS and SARS-CoV-2 are similar, but structural differences in the receptor binding domain (RBD) preclude the use of SARS-specific neutralizing antibodies to inhibit SARS-CoV-2. Here we used comparative pangenomic analysis of all sequenced reference Betacoronaviruses, complemented with functional and structural analyses. This analysis reveals that, among all core gene clusters present in these viruses, the envelope protein E shows a variant cluster shared by SARS and SARS-CoV-2 with two completely-conserved key functional features, namely an ion-channel, and a PDZ-binding motif (PBM). These features play a key role in the activation of the inflammasome causing the acute respiratory distress syndrome, the leading cause of death in SARS and SARS-CoV-2 infections. Together with functional pangenomic analysis, mutation tracking, and previous evidence, on E protein as a determinant of pathogenicity in SARS, we suggest E protein as an alternative therapeutic target to be considered for further studies to reduce complications of SARS-CoV-2 infections in COVID-19.Next-generation sequencing (NGS) has instigated the research