Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the "flu" in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) is the most significant because it causes recurring seasonal epidemics, occasional pandemics, and zoonotic outbreaks in human populations, globally. The host innate immune response to IAV infection plays a critical role in sensing, preventing, and clearing the infection as well as in flu disease pathology. Host cells sense IAV infection through multiple receptors and mechanisms, which culminate in the induction of a concerted innate antiviral response and the creation of an antiviral state, which inhibits and clears the infection from host cells. However, IAV antagonizes and escapes many steps of the innate antiviral response by different mechanisms. Herein, we review those host and viral mechanisms. This review covers most aspects of the host innate immune response, i.e., (1) the sensing of incoming virus particles, (2) the activation of downstream innate antiviral signaling pathways, (3) the expression of interferon-stimulated genes, (4) and viral antagonism and escape.

Novel antioxidant protein target therapy to counter the prevalence and severity of SARS-CoV-2.

Background: This review analyzed the magnitude of the COVID-19 pandemic globally and in India and the measures to counter its effect using natural and innate immune booster molecules. The study focuses on two phases: the first focuses on the magnitude, and the second on the effect of antioxidants (natural compounds) on SARS-CoV-2. Methods: The magnitude of the prevalence, mortality, and comorbidities was acquired from the World Health Organization (WHO) report, media, a report from the Ministry of Health and Family Welfare (MoHFW), newspapers, and the National Centre of Disease Control (NCDC). Research articles from PubMed as well as other sites/journals and databases were accessed to gather literature on the effect of antioxidants. Results: In the elderly and any chronic diseases, the declined level of antioxidant molecules enhanced the reactive oxygen species, which in turn deprived the immune system. Conclusion: Innate antioxidant proteins like sirtuin and sestrin play a vital role in enhancing immunity. Herbal products and holistic approaches can also be alternative solutions for everyday life to boost the immune system by improving the redox balance in COVID-19 attack. This review analyzed the counteractive effect of alternative therapy to boost the immune system against the magnitude of the COVID-19 pandemic.

Edelfosine reactivates latent HIV-1 reservoirs in myeloid cells through activation of NF-κB and AP1 pathway.

The persistence of latent HIV-1 reservoirs in cells presents a formidable challenge towards a complete HIV cure. Edelfosine is an FDA-approved investigational, anti-neoplastic drug. In this study, we aimed to investigate its role as a HIV-1 Latency Reversal Agent (LRA) using latency model cell lines. Our findings demonstrated that edelfosine reactivated latent HIV-1 viruses in myeloid cells in a dose and time-dependent manner. The mechanism of reactivation by edelfosine involved the activation of NF-κB and AP1 pathways in these cells. The reactivated virus was non-infectious. Delineating the mechanism of non-infectious virus production revealed an increased stabilization of cellular APOBEC3G protein as well as its enhanced incorporation into the released viruses. Thus, our study demonstrated for the first time an additional role of edelfosine in reactivation of latent HIV-1 and production of non-infectious virus. Our results have paved the way for repurposing of edelfosine as a novel HIV-1 latency reversal agent.

Critical pathways of oral squamous cell carcinoma: molecular biomarker and therapeutic intervention.

The rapid growth of oral cancer is a significant concern, especially in developing countries due to the advanced lifestyle and 5-year survival despite advanced multimodality of cancer care. The poor modality might be due to the detection of disease in the advanced stage. Early detection and development of novel therapies can improve oral cancer patient survival. The PI3K/AKT/mTOR and RAS-RAF-MEK-ERK are very extensively exploited pathways in oral cancer. These pathways are very critical in the progression of tumorigenesis in oral cancer. This review focuses on the association of Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways in terms of protein expression level, genetic mutation, and therapeutic intervention in oral cancer.

Biofilms: Architecture, Resistance, Quorum Sensing and Control Mechanisms.

Biofilm is a mode of living employed by many pathogenic and environmental microbes to proliferate as multicellular aggregates on inert inanimate or biological substrates. Several microbial diseases are associated with biofilms that pose challenges in treatment with antibiotics targeting individual cells. Bacteria in biofilms secrete exopolymeric substances that contribute to architectural stability and provide a secure niche to inhabiting cells. Quorum sensing (QS) plays essential roles in biofilm development. Pathogenic bacteria in biofilms utilize QS mechanisms to activate virulence and develop antibiotic resistance. This review is a brief overview of biofilm research and provides updates on recent understandings on biofilm development, antibiotic resistance and transmission, and importance of QS mechanisms. Strategies to combat biofilm associated diseases including anti-biofilm substances, quorum quenching molecules, bio-surfactants and competitive inhibitors are briefly discussed. The review concludes with updates on recent approaches utilized for biofilm inhibition and provides perspectives for further research in the field.