BTN3A3 evasion promotes the zoonotic potential of influenza A viruses.

Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic. Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans.

Low pathogenic avian influenza virus infection retards colon microbiota diversification in two different chicken lines.

Background: A commensal microbiota regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiota population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted.

Methods: Colon samples were taken from control and infected groups at various timepoints post infection.

Middle East respiratory syndrome: pathogenesis and therapeutic developments.

The first case of Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in the year 2012, which spread rapidly and increased to more than 2200 in 2018. This highly pathogenic virus with high mortality rate is among one of the major public health concerns. Saudi Arabia remains to be the most affected region with the majority of MERS-CoV cases, and currently, no effective drugs and vaccines are available for prevention and treatment.

Viral priming of cell intrinsic innate antiviral signaling by the unfolded protein response.

The innate response to a pathogen is critical in determining the outcome of the infection. However, the interplay of different cellular responses that are activated following viral infection and their contribution to innate antiviral signalling has not been clearly established. This work shows that flaviviruses, including Dengue, Zika, West Nile and Tick-borne encephalitis viruses, activate the unfolded protein response before transcription of interferon regulatory factor 3 induced genes.

Cellular Targets for the Treatment of Flavivirus Infections.

Classical antiviral therapy targets viral functions, mostly viral enzymes or receptors. Successful examples include precursor herpesvirus drugs, antiretroviral drugs that target reverse transcriptase and protease, influenza virus directed compounds as well as more recent direct antiviral agents (DAA) applied in the treatment of hepatitis C virus (HCV). However, from early times, the possibility of targeting the host cell to contain the infection has frequently re-emerged as an alternative and complementary antiviral strategy.

A method for the detection of virus infectivity in single cells and real time: Towards an automated fluorescence neutralization test.

Virus neutralizing antibodies are critical correlates of protection in vaccine development and are discriminatory in the plaque reduction neutralization test when used for the diagnosis of viral infections. However, neutralization assays are time consuming, labor intensive and highly variable, thus limiting their use. Advances in automated live imaging of cells opened new possibilities for standard virus diagnostic techniques such as neutralization assays.

Induction of Transcriptional Gene Silencing by Expression of shRNA Directed to c-Myc P2 Promoter in Hepatocellular Carcinoma by Tissue-Specific Virosomal Delivery.

Double-stranded RNA-mediated transcriptional gene silencing (TGS) has shown promising results over posttranscriptional gene silencing (PTGS) due to its long term and heritable nature. Various research groups have shed light on different mechanisms by which TGS operate. Some of these include histone modification, DNA methylation, or restriction of RNA polymerase binding onto the target gene's promoter.

The host cell response to tick-borne encephalitis virus.

Tick-borne encephalitis virus is the most prevalent autochthonous arbovirus in Europe and an important travel-associated virus. Complications of the infection could lead to lethal encephalitis in susceptible individuals. However, despite its clinical relevance and expanding geographical distribution, most of our knowledge on its pathogenesis is inferred from studies on other flaviviruses.

A novel placental like alkaline phosphatase promoter driven transcriptional silencing combined with single chain variable fragment antibody based virosomal delivery for neoplastic cell targeting [corrected].

Background: Placental like alkaline phosphatase (PLAP), an oncofetal antigen, is highly expressed in germ cell, cervical, ovarian and several other tumour types but minimally in normal tissues [corrected]. The expression of a PLAP promoter based transcriptional unit following antigen mediated cell specific delivery is a possible approach for tumour targeting.

Methods: PLAP promoter alone or in combination with NFκB DNA response elements was used for expressing shRNA targeting the long control region (LCR) of human papillomavirus (HPV)-16 oncogenes E6 and E7 via transcriptional gene silencing in PLAP expressing cervical cancer cell lines, SiHa and CaSki.

Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by cancer in the modern world and majority of the cases are related to chronic hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional protein of 17 kDa which modulates several cellular processes by direct or indirect interaction with a repertoire of host factors resulting in HCC.

Combination of hepatocyte specific delivery and transformation dependent expression of shRNA inducing transcriptional gene silencing of c-Myc promoter in hepatocellular carcinoma cells.

Background: A specific targeting modality for hepatocellular carcinoma (HCC) could ideally encompass a liver cell specific delivery system of a transcriptional unit that is active only in neoplastic cells. Sendai virosomes, derived from Sendai viral envelopes, home to hepatocytes based on the liver specific expression of asialoglycoprotein receptors (ASGPRs) which are recognized by the Sendai virosomal fusion (F) proteins. As reported earlier by us and other groups, transcriptional gene silencing (TGS) does not require continuous presence of the effector siRNA/shRNA molecule and is heritable, involving epigenetic modifications, leading to long term transcriptional repression.