Occult hepatitis B virus infection and current perspectives on global WHO 2030 eradication.

The current World Health Organization (WHO) Hepatitis Elimination Strategy suffers from lack of a target for diagnosing or expunging occult HBV infection. A sizable segment of the global population has an undetected HBV infection, particularly the high-risk populations and those residing in countries like India with intermediate endemicity. There is growing proof that people with hidden HBV infection can infect others, and that these infections are linked to serious chronic hepatic complications, especially hepatocellular carcinoma. Given the current diagnostic infrastructure in low-resource settings, the WHO 2030 objective of obliterating hepatitis B appears to be undeniably challenging to accomplish. Given the molecular basis of occult HBV infection strongly linked to intrahepatic persistence, patients may inexplicably harbour HBV genomes for a prolonged duration without displaying any pronounced clinical or biochemical signs of liver disease, and present histological signs of moderate degree necro-inflammation, diffuse fibrosis, and hence the international strategy to eradicate viral hepatitis warrants inclusion of occult HBV infection.

Genomic surveillance of omicron B.1.1.529 SARS-CoV-2 and its variants between December 2021 and March 2023 in Tamil Nadu, India-A state-wide prospective longitudinal study.

A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.

Application of probiotics in cervical cancer infections to enhance the immune response.

Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70 % of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17 % cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials.

HIV-Encoded Gene Therapy as Anti-cancer Therapeutics: A Narrative Review.

Recently, there has been interest in using viruses as cancer treatments. Oncolytic virology was founded by scientists who noticed that viruses might preferentially lyse cancer cells over healthy ones. Oncolytic virotherapy has similar obstacles as other treatment approaches, gaining entry into the specific tumour cell, encountering antiviral immune responses, off-target infection and many other unfavourable circumstances in the tumour microenvironment, and a lack of unique therapeutic and predictive biomarkers. However, oncolytic viruses have emerged as the main players in the biological treatment for cancer with the use of vectors such as human adenoviruses in oncolytic virotherapy. Recent large-scale research has shown that other viruses, such as the measles virus and the herpes simplex virus (HSV), may potentially be viable options for cancer treatment. The FDA has cleared T-VEC, an HSV-based oncolytic virus, for use in biological cancer treatment after its successful completion of human clinical trials. Furthermore, the measles virus vaccine strain has shown remarkable outcomes in pre-clinical and clinical testing. The use of such modified viruses in biological cancer treatment holds promise for groundbreaking discoveries in the field of cancer research because of their therapeutic effectiveness, fewer side effects, and safety. Several other newer approaches have been used in recent years. HIV-encoded proteins are also hypothesized to promote mitochondrial homeostasis causing bystander-induced apoptosis. We provide an overview of the most recent developments in the clinical use of oncolytic virus-based biological cancer treatment in this study. This evaluation also assesses the advantages and disadvantages of the viral candidates and provides insight into their potential in the future.

Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors.

BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.

Human Immunodeficiency Virus-Human Pegivirus Coinfected Individuals Display Functional Mucosal-Associated Invariant T Cells and Follicular T Cells Irrespective of PD-1 Expression.

Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4lo, CD4hi, and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIV+HPgV+ individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV-. HIV/HPgV coinfection was significantly associated with increased absolute CD4+ T cell counts. HIV+HPgV+ and HIV+HPgV- individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4+ and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, and CXCR5+CD4+ T cells and CXCR5+CD8+ T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4+ T and CD8+ T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4+ MAIT and CD8+ MAIT cells. Decrease in absolute CD4+ T cell counts correlated positively with intracellular IFN-γ levels by CD4lo T cells, whereas increase of the same correlated negatively with TNF-α in the CD4lo T cells of HIV+HPgV+ individuals. HIV/HPgV coinfected individuals display functional CD4+ and CD8+ MAIT, TFH, and TFC cells irrespective of PD-1 expression.

Serosurveillance of dengue infection and correlation with mosquito pools for dengue virus positivity during the COVID-19 pandemic in Tamil Nadu, India - A state-wide cross-sectional cluster randomized community-based study.

Background: Dengue is a vector-borne viral disease impacting millions across the globe. Nevertheless, akin to many other diseases, reports indicated a decline in dengue incidence and seroprevalence during the COVID-19 pandemic (2020-22). This presumably could be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to vectors due to lockdowns. Scientific evidence on dengue virus (DENV) disease during the COVID-19 pandemic is limited globally. Methods: A cross-sectional, randomized cluster sampling community-based survey was carried out to assess anti-dengue IgM and IgG and SARS-CoV-2 IgG seroprevalence across all 38 districts of Tamil Nadu, India. The prevalence of DENV in the Aedes mosquito pools during 2021 was analyzed and compared with previous and following years of vector surveillance for DENV by real-time PCR. Findings: Results implicate that both DENV-IgM and IgG seroprevalence and mosquito viral positivity were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3·76% of mosquito pools were positive for DENV. In the human sera, 4·12% were positive for DENV IgM and 6·4% were positive for DENV IgG. The anti-SARS-CoV-2 antibody titres correlated with dengue seropositivity with a significant association whereas vaccination status significantly correlated with dengue IgM levels. Interpretation: Continuous monitoring of DENV seroprevalence, especially with the evolving variants of the SARS-CoV-2 virus and surge in COVID-19 cases will shed light on the transmission and therapeutic attributes of dengue infection.

Emergence of SARS-CoV-2 omicron variant JN.1 in Tamil Nadu, India - Clinical characteristics and novel mutations.

In December 2023, we observed a notable shift in the COVID-19 landscape, when JN.1 omicron emerged as the predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive clinical specimens, followed by sequence analysis. Mutations within the spike protein sequences were analysed and compared with the previously reported lineages and sub-lineages, to identify the potential impact of the unique mutations on protein structure and possible alterations in the functionality. Several unique and dynamic mutations were identified herein. Molecular docking analysis showed changes in the binding affinity, and key interacting residues of wild-type and mutated structures with key host cell receptors of SARS-CoV-2 entry viz., ACE2, CD147, CD209L and AXL. Our data provides key insights on the emergence of newer variants and highlights the necessity for robust and sustained global genomic surveillance of SARS-CoV-2.

Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations.

In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.