Flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. The prominent viruses of this group include dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus tick borne encephalitis virus and Zika Virus. These are endemic in many parts of the world. They are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. NS1 is a highly conserved non-structural protein among flaviviruses, which exist in diverse forms. The intracellular dimer form of NS1 plays role in genome replication, whereas, the secreted hexamer plays role in immune evasion. The secreted NS1 has been identified as a potential diagnostic marker for early detection of the infections caused by flaviviruses. In addition to the diagnostic marker, the importance of NS1 has been reported in the development of therapeutics. NS1 based subunit vaccines are at various stages of development. The structural details and diverse functions of NS1 have been discussed in detail in this review.

Japanese encephalitis virus (JEV) is a plus strand RNA virus, which infects brain. MicroRNAs are regulatory non-coding RNAs which regulate the expression of various genes in cells. Viruses modulate the expression of various microRNAs to suppress anti-viral signaling and evade the immune response. SOCS (Suppressor of cytokine signalling) family of proteins are negative regulators of anti-viral Jak-STAT pathway. In this study, we demonstrated the regulatory role of SOCS5 in Jak-STAT signaling and its exploitation by JEV through a microRNA mediated mechanism. JEV infection in human brain microglial cells (CHME3) downregulated the expression of miR-432, and upregulated SOCS5 levels. SOCS5 was validated as a target of miR-432 by using 3′UTR clone of SOCS5 in luciferase vector along with miR-432 mimic. The overexpression of miR-432 prior to JEV infection enhanced the phosphorylation of STAT1 resulting into increased ISRE activity and cellular inflammatory response resulting into diminished viral replication. The knockdown of SOCS5 resulted into increased STAT1 phosphorylation and suppressed viral replication. JEV infection mediated downregulation of miR-432 leads to SOCS5 upregulation, which helps the virus to evade cellular anti-viral response. This study demonstrated that JEV utilizes this microRNA mediated strategy to manipulate cellular immune response promoting JEV pathogenesis.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the group of Betacoronaviruses. The SARS-CoV-2 is closely related to SARS-CoV-1 and probably originated either from bats or pangolins. SARS-CoV-2 is an etiological agent of COVID-19, causing mild to severe respiratory disease which escalates to acute respiratory distress syndrome (ARDS) or multi-organ failure. The virus was first reported from the animal market in Hunan, Hubei province of China in the month of December, 2019, and was rapidly transmitted from animal to human and human-to-human. The human-to-human transmission can occur directly or via droplets generated during coughing and sneezing. Globally, around 53.9 million cases of COVID-19 have been registered with 1.31 million confirmed deaths. The people > 60 years, persons suffering from comorbid conditions and immunocompromised individuals are more susceptible to COVID-19 infection. The virus primarily targets the upper and the lower respiratory tract and quickly disseminates to other organs. SARS-CoV-2 dysregulates immune signaling pathways which generate cytokine storm and leads to the acute respiratory distress syndrome and other multisystemic disorders.