Pathogenic and Genotypic Characterization of a Japanese Encephalitis Virus Isolate Associated with Reproductive Failure in an Indian Pig Herd.

BACKGROUND:India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS:This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. CONCLUSIONS/SIGNIFICANCE:Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of suitable strategies to control JE in India

Phylogenetic analysis for the prM gene of JEV.

<p>The tree was constructed with MEGA6 software using neighbor-joining method based on the kimura-2 parameter model. Data are based on a bootstrap value of 1000 and cutoff value of 50.</p

Need of booster vaccine doses to counteract the emergence of SARS-CoV-2 variants in the context of the Omicron variant and increasing COVID-19 cases: An update

The emergence of different variants of SARS-CoV-2, including the Omicron (B.1.1.529) variant in November 2021, has resulted in a continuous major health concern at a global scale. Presently, the Omicron variant has spread very rapidly worldwide within a short time period. As the most mutated variant of SARS-CoV-2, Omicron has instilled serious uncertainties on the effectiveness of humoral adaptive immunity generated by COVID-19 vaccination or an active viral infection as well as the protection provided by antibody-based immunotherapies. Amidst such high public health concerns, the need to carry out booster vaccination has been emphasized. Current evidence reveals the importance of incorporating booster vaccination using several vaccine platforms, such as viral vector- and mRNA-based vaccines, as well as other platforms that are under explorative investigations. Further research is being conducted to assess the effectiveness and durability of protection provided by booster COVID-19 vaccination against Omicron and other SARS-CoV-2 variants

Comparative analysis of critical amino acids in the E protein associated with JEV neurovirulence.

<p>Eight amino acids in the E protein critical for neurovirulence in the vaccine strain (SA14-14-2) and other JEV strains including current swine isolate.</p

Phylogenetic analysis for prM gene of JEV including sequences data from Indian JEV isolates only.

<p>The tree was constructed with MEGA6 software using neighbor-joining method based on the kimura-2 parameter model. Data are based on a bootstrap value of 1000 and cutoff value of 50.</p

Sows which delivered JEV positive stillborn piglets in a herd.

<p>Out of 28 sows that farrowed in a herd, 10 sows delivered stillborn piglets. Sow number, date of farrowing, breed, number of stillbirth and RT-PCR results for JEV are presented.</p

Gene targets and nucleotide sequences of primers used to amplify JEV gene segments.

<p>Gene targets and nucleotide sequences of primers used to amplify JEV gene segments.</p

Phylogenetic analysis for the E gene of JEV.

<p>The tree was constructed with MEGA6 software using neighbor-joining method based on the kimura-2 parameter model. Data are based on a bootstrap value of 1000 and cutoff value of 50.</p

SIRT2 deacetylase represses NFAT transcription factor to maintain cardiac homeostasis

Heart failure is an aging-associated disease that is the leading cause of death worldwide. Sirtuin family members have been largely studied in the context of aging and aging-associated diseases. Sirtuin 2 (SIRT2) is a cytoplasmic protein in the family of sirtuins that are NAD(+)-dependent class III histone deacetylases. In this work, we studied the role of SIRT2 in regulating nuclear factor of activated T-cells (NFAT) transcription factor and the development of cardiac hypertrophy. Confocal microscopy analysis indicated that SIRT2 is localized in the cytoplasm of cardiomyocytes and SIRT2 levels are reduced during pathological hypertrophy of the heart. SIRT2-deficient mice develop spontaneous pathological cardiac hypertrophy, remodeling, fibrosis, and dysfunction in an age-dependent manner. Moreover, young SIRT2-deficient mice develop exacerbated agonist-induced hypertrophy. In contrast, SIRT2 overexpression attenuated agonist-induced cardiac hypertrophy in cardiomyocytes in a cell-autonomous manner. Mechanistically, SIRT2 binds to and deacetylates NFATc2 transcription factor. SIRT2 deficiency stabilizes NFATc2 and enhances nuclear localization of NFATc2, resulting in increased transcription activity. Our results suggest that inhibition of NFAT rescues the cardiac dysfunction in SIRT2-deficient mice. Thus, our study establishes SIRT2 as a novel endogenous negative regulator of NFAT transcription factor