Leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity) and sphingomyelin (the SMase activity). Recent studies of a L. major ISCL-null mutant (iscl−) indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl− mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl− promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl−. These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host.

The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment in health, social, economic, scientific, and medical sectors across the globe. Owing to the not so well understood mechanism of disease pathogenesis in terms of variations in immune responses, there remains obscure why some of the patients who are infected by the novel SARS-CoV-2 develop an unpredictable clinical course that rapidly causes severe and deadly complications/manifestations. Currently, several assays are available for the confirmation of SARS-CoV-2 infection at the point of care. However, none of these assays can predict the severity of the COVID-19 disease. Thus, the identification of a prognostic biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease could enable the clinicians for more efficient patient triage and treatment. In this regard, the present review describes the role of selected biomolecules that are crucially involved in the immune-pathogenesis of SARS-CoV-2 infection such as hyper-immune responsiveness, bradykinin storm and vascular leakage assuming these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based on the review, we also propose the development of a cost-effective SERS-based prognostic biosensor for the detection and quantification of biomolecules for use as a point-of-care system during a disease outbreak.

RNA interference (RNAi) refers to the process of post-transcriptional silencing of cellular mRNA by the application of double-stranded RNA (dsRNA). RNAi strategies have been widely employed to regulate gene expression in plants and animals including insects. With the availability of the full genome sequences of major vector mosquitoes, RNAi has been increasingly used to conduct genetic studies of human pathogens in mosquito vectors and to study the evolution of insecticide resistance in mosquitoes. This review summarizes the recent progress in our understanding of mosquito-pathogen interactions using RNAi and various methods of dsRNA delivery in mosquitoes at different stages. We also discuss potential applications of this technology to develop novel tools for vector control.

Novel SARS-CoV-2 named due to its close homology with severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiologic agent for the ongoing pandemic outbreak causing loss of life and severe economic burden globally. The virus is believed to be evolved in a recombined form of bat and animal coronavirus with the capacity to infect human host using the ACE2 receptors as an entry point. Though the disease pathogenesis is not elucidated completely, the virus-mediated host response retains a similar pattern to that of previous SARS-CoV. Based on the available trend it is assumed that pediatric groups are less susceptible to the coronavirus. Understanding the possible mechanism that protects the children from hyper-inflammatory or disease severity could lead to better treatment modalities. In the present review, we have discussed the significance of age and sex-dependent pattern of ACE2 receptor expression and ACE2 variants in the immune protective mechanism of the disease virulence. We have also added a brief note on the importance of sex hormones in the pathogenesis of ACE2 mediated SARS-CoV2 infection.

Platelet activation has been reported to play a major role in inflammatory response and thrombocytopenia during dengue viral infection. Cells expressing FcϒR2Aand DC-SIGN receptors are reported to be involved in dengue virulence. The present study is designed to assess the expression level of these two receptors on platelet surface collected from dengue patients and to study its association in patients with platelet RNA positive for dengue virus. This was an analytical cross-sectional study carried out in JIPMER hospital, Puducherry. Forty-four patients with dengue infection as cases and 44 patients with non dengue acute other febrile illness(OFI) as controls were recruited. Peripheral venous blood was withdrawn on day of admission, day 3 post admission and day of discharge and serological tests for NS1 dengue antigen and anti IgM antibody were analyzed for diagnosis of dengue infection. Platelet rich plasma was assessed for DC SIGN, FcϒR2A levels and platelets separated from dengue patients were subjected to RNA extraction and detection of presence of viral RNA. The study observed a decreased expression of DC-SIGN and FcϒR2A on platelets in dengue patients compared to OFI group on all the time points. Further, cells expressing DC-SIGN and FcϒR2A were found to be decreased on platelets in dengue patients who were positive for NS1 antigen. DC-SIGN and FcϒR2A expression was also found to be notably decreased in patients positive for platelet DENV RNA when compared with patients negative for platelet DENV RNA. Our results suggest that DC-SIGN and FcϒR2A, which are receptors for viral capture and immune mediated clearance respectively, might be down regulated on platelets in patients with dengue infection. The decreased receptor expression diminishes platelet activation and subsequently has protective action on the host from the ongoing conflict between immune system and dengue virus.