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Production of biofuel from Lignocellulosic biomass (LCB) reduces the energy dependency on fossil fuels. The process of manufacture does not have any adverse environmental impact. LCB is an abundant and promising renewable resource for long term biofuel supply. Bioethanol derived from LCB has the potential to meet the current energy demand, reduces greenhouse gases and supports rural economy. Cellulosic ethanol is one of the viable energy sources and therefore, it is considered as an alternative fuel. A lot of efforts have been made in the last decades on production of ethanol from cellulosic source as cost competitive with conventional fossil fuel. The production of bioethanol involves three steps: pretreatment, hydrolysis and fermentation. Pretreatment of LCB is usually done following physical, chemical or physicochemical process. Hydrolysis is carried out either chemically or enzymatically followed by microbial fermentation. However, involvement of costly equipment, high energy consumption and generation of toxic substances need to be evaluated. This drives the attention of scholars in the field towards alternative option for the development and optimization of biological methods of pretreatment, hydrolysis and fermentation. In this review we focus on recent developments of biological methods of pretreatment, hydrolysis and fermentation with respect to their advantages and limitations.

Primary effusion lymphoma (PEL) is an aggressive form of non-Hodgkin lymphoma of B cells caused by Kaposi's Sarcoma-associated Herpes Virus (KSHV). KSHV encoded latent and lytic antigens promote oncogenic transformation and evade apoptosis through the modulation of various host cellular signaling pathways. Nm23-H1 is a known metastatic suppressor whose expression inversely correlates with the metastatic potential of different cancers. Here, we set out to assess the role of Nm23-H1 in PEL development.Flow cytometry and real-time PCR assays were performed for Nm23-H1 expression analysis. Induction of apoptosis was assessed using Western blotting and flow cytometry-based assays in Nm23-H1 overexpressing cells. Co-immunoprecipitation assays, confocal microscopy and imaging flow cytometry were performed to determine Nm23-H1 and vFLIP K13 protein-protein interaction. A PEL cell-induced xenograft model was established in non-obese diabetic/severely combined immunodeficient (NOD/SCID) mice to validate the effect of Nm23-H1 overexpression.We found that Nm23-H1 expression was significantly downregulated both at transcriptional and protein levels in PEL cell lines and that its overexpression triggered mitochondrial-mediated caspase-dependent apoptosis. We revealed Nm23-H1 interacts with the latent protein vFLIP K13 and that Nm23-H1 overexpression leads to inhibition of vFLIP K13 driven nuclear factor-kappa B (NF-κB) signaling with concurrent inhibition of autocrine and paracrine growth factors and downregulation of latent KSHV antigens without induction of active lytic reactivation. We also confirmed the effects of Nm23-H1 overexpression in a PEL cell-induced xenograft model in NOD/SCID mice.Downregulation of Nm23-H1 expression in KSHV-infected PEL cells and its overexpression trigger apoptosis by impairing vFLIP K13-driven NF-κB signaling, suggesting therapeutic implications of Nm23-H1 for primary effusion lymphomas.

Hibiscus rosa sinensis has an infinite resource of phytochemicals and has emerged as a solution for different health-related issues such as anti-diabetic, anti-microbial and wound healing activity as proved in past clinical studies. Focusing on the current situation, an incessant increase in daily COVID-19 cases and the struggle to discover effective treatment measures for SARS-CoV-2 had led to a global health catastrophe. Upsurge in COVID-19 cases had revealed a pattern characterised as a first, second, third wave and beyond. This cycle of new SARS-CoV-2 variant transmission needed to be terminated by selecting a favourable effective target, and the 3CL protease enzyme (3CLpro or Mpro) of SARS-CoV-2 acts as a possible target. The objective of this study is to investigate the phytochemicals identified in Hibiscus rosa sinensis flowers for their potential anti-SARS-CoV-2 properties virtually, targeting the 3CLpro or Mpro, which regulates viral pathogenesis. The present research protocol includes molecular docking of 34 phytochemicals identified from the Hibiscus rosa sinensis flower and targeted against the active site of the 3CLpro enzyme. Computational analysis revealed that the top 3 ligands: cyanidin-3-sophoroside-5-glucoside (-10.9 kcal/mol), 1,2-benzenedicarboxylic acid isodecyl octyl ester (-10.1 kcal/mol) and rutin (-9.3 kcal/mol) had better binding affinity as compared to the control inhibitor remdesivir (-8 kcal/mol). Further investigation in terms of ligand-protein interaction, physiochemical, ADMET and drug-likeness parameters showed that cyanidin-3-sophoroside-5-glucoside possessed promising properties and could act as a potentially effective drug candidate. However, our study needs to be supported by in vitro and in vivo evaluations to determine the precise mechanism of inhibitory action.

Background: The association of BAX -248 G>A and BCL2 -938 C>A with different cancers created conflicts. We studied the correlation and the effect of these polymorphisms in patients with Nasopharyngeal Carcinoma (NPC). Methods: PCR-RFLP and Sanger sequencing were used to detect polymorphisms. Statistical analysis including forest plot and Kaplan-Meier Log-rank test was conducted to investigate the association and effect of these SNPs on the NPC patients’ survival. The computational study was performed to investigate the possible regulatory role between these polymorphisms and the poor survival of NPC patients. Meta-analysis was executed to check the tissue-specific association of these polymorphisms in the context of global cancer prognosis. Results: We observed an increased and significant association of BAX -248 G>A [GA:OR=5.29, 95%CI=1.67,16.67, P=0.004; GA+AA:OR=5.71, 95%CI=1.82,17.90, P =0.002; A:OR=5.33, 95%CI=1.76,16.13, P=0.003], and BCL2 -938 C>A [CA:OR=2.26, 95%CI=1.03,4.96, P=0.04; AA:OR=3.56, 95%CI=0.97,13.05, P=0.05; CA+AA:OR=3.10, 95%CI=1.51,6.35, P=0.002; A:OR=2.90, 95% CI=1.59,5.29, P=0.0005] with the risk of NPC. Also, these SNPs were strongly correlated with poor survival in NPC patients (lower estimated survival mean, lower estimated proportion surviving at 5 years with pA showed a significant correlation with carcinomas [A vs G:OR=1.60, 95%CI=1.09,2.34, P=0.01; AA vs GG:OR=2.61, 95%CI=1.68,4.06, PA with other malignancies [A vs C:OR=1.45, 95%CI=1.26,1.66, PA and BCL2 -938 C>A was associated with poor survival in NPC patients. It may increase cancer susceptibility through transcriptional regulation. Moreover, these SNPs’ effects could be tissue-specific.

Nasopharyngeal Carcinoma (NPC) is one of the leading cancers in India's north-eastern (NE) region affecting a section of the population each year. A proportion of the NPC cases are observed to recur even after therapy, indicating the involvement of other factors. We aimed to explore the NPC and Epstein-Barr virus (EBV) burden in the NE region and investigate the prognostic factors for the NPC patients' poor survival and recurrence. NPC patients' information was obtained from different state hospitals between 2014 and 2019. PCR and Sanger sequencing were performed to detect EBV types. Statistical analysis, including forest plot analysis, Kaplan-Mayer survival plot, Log-rank test, cox hazard regression, and Aalen's additive regression model, were performed to determine prognostic factors for the NPC patients' lower survival and recurrence. We observed an increased incidence of NPC and EBV infection in the past five years. Step-wise statistical analyses pointed out that variable such as non-professionals (B = 1.02, HR = 2.8, 95%CI = 1.5,4.9) workers (B = 0.92, HR = 2.5, 95%CI = 1.4,4.4), kitchen cum bedroom (B = 0.61, HR = 1.8, 95%CI = 1.2,2.8), mosquito repellent (B = 0.60, HR = 1.7, 95%CI = 1.1,2.7), nasal congestion (B = 0.60, HR = 1.8, 95%CI = 1.2,2.8), lower haemoglobin level (B = 0.92, HR = 2.5, 95%CI = 1.3,4.9), tumor stage IV (B = 2.8, HR = 1.8, 95%CI = 1.6,14.3), N2 (B = 1.4, HR = 4.0, 95%CI = 1.8,9.1), N3 (B = 1.9, HR = 6.4, 95%CI = 2.8,15.3), and M+ (B = 2.02, HR = 7.5, 95%CI = 4.1,13.7) revealed significant correlation with NPC patients' poor prognosis (p 0.05). The presence of viral factors also showed a significant association with NPC patients' decreased survival. We concluded that factors related to day-to-day life with EBV infection could be the individual predictor for NPC incidence, lower survival, and disease recurrence.The online version contains supplementary material available at 10.1007/s13337-022-00789-5.

Objective: To establish effectiveness between Double Disk Synergy Test (DDST) and Inhibitory Potentiated Disk Diffusion Test (IPDDT) for detection of ESBL isolates.Material and Method: Total two hundred screened isolation of E. coli and Klebsiella species obtained from 3146 various clinical samples such as pus, urine, blood, CSF, ear discharge, pleural fluid & sputum were included in the study. ESBL production where detected by Double Disk Synergy Test (DDST) and Inhibitory Potentiated Disk Diffusion Test (IPDDT) as per CLSI guidelines.Results: 200 isolates 117(58.5 %) E.coli and 83(41.5%) Klebsiella were identified.By DDST test 92.6% & 89.1%,66.7% & 71.7%,88.8% & 71.7% showed synergy between Ceftazidime, Cefotaxime, Ceftriaxone and Amoxicillin with Clavulanic acid by Klebsiella species and E.coli respectively.By IPDDT test 27.7% & 40.1%,28.9% & 43.4% and 36.1% & 44.4% showed synergy between Ca Vs Ca/C , Ce Vs Ce/C ,Ca Vs Ca/C + Ce Vs Ce/C by Klebsiella species and E.coli respectively.The ESBL isolate detected by DDST was 73(36.5%) and by IPDDT was 82 (41%). Conclusion: Additional 4.5% (9) ESBL isolates detected by IPDDT than DDST. ESBL detection have a significant impact on several important clinical outcomes. ESBLs outbreaks require accurate and precise detection.

Objectives Mannose-binding lectin (MBL), an essential innate immune molecule, enhances the opsonization process and activates the complement system. Genetic variations at the promoter and coding region of the MBL-2 gene have been associated with susceptibility to systemic lupus erythematosus (SLE); however, reports remained inconsistent. The present study performs a meta-analysis of published peer-reviewed articles to draw a definitive conclusion. Materials and Methods Published peer-reviewed articles on the association of MBL-2 gene polymorphisms and SLE were screened on various databases such as PubMed (Medline), ScienceDirect, and Google Scholar. A total of 23 eligible articles were included in the present study, comprising 3074 SLE patients and 3985 controls. Genotype and/or allele data for MBL-2 polymorphisms (A > B, A > C, A > D, A > O, Y > X and H > L) were extracted and analyzed by Comprehensive Meta-Analysis software (CMA V3.1). Results The overall analysis revealed a significant association of MBL-2 (A > O) polymorphism with a predisposition to SLE in allele contrast ( p = 0.000; OR = 1.261), homozygous ( p = 0.005; OR = 1.482), heterozygous ( p = 0.004; OR = 1.247), dominant ( p = 0.000; OR = 1.303) and recessive ( p = 0.025; OR = 1.356) genetic comparison model. Similar results were also observed in the comparison of allele and the dominant genetic model of MBL-2 (A > B) polymorphism in overall (allele: p = 0.000, OR = 1.46, dominant: p = 0.001, OR = 1.31) and in the Asian cohorts (allele: p = 0.007, OR = 1.43, dominant: p = 0.008, OR = 1.32). Interestingly, MBL-2 (Y-221X) polymorphism exhibited protection against the development of SLE in heterozygous ( p = 0.005, OR = 0.619) and dominant genetic comparison ( p = 0.01, OR = 0.672) models. Conclusions MBL-2 variants (A > O and A > B) are associated with predisposition to SLE. Conversely, promoter polymorphism (Y-221X) offers protection against SLE development.

Control of stage specific spike in ethylene production at anthesis has been a vauable route to potentially enhance genetic ceiling for grain filling of rice spikelet. A number of genes controlling ethylene homeostasis and starch synthesis have been identified so long, but lack of credible information on master modulation of gene expression by miRNAs and their target genes associated with hormonal dynamics obfuscate mechanisms controlling genotype difference in quantum of grain filling. The confusion accounts for consequent shrinkage of options for yield manipulation. In a two by two factorial design, miRNA regulation of spikelet specific grain development in low against high sterile recombinant inbred lines of rice Oryza sativa L. namely CR 3856-62-11-3-1-1-1-1-1-1 (SR 157) and CR 3856-63-1-1-1-1-1-1-1 (SR 159) respectively, and inferior verses superior spikelets were compared during first 10 days after anthesis. Grain filling was poorer in SR159 than SR157 and inferior spikelets in the former were most vulnerable. Between the cultivars, overall expression of unique miRNAs with targets on ethylene pathway genes was higher in SR159 than SR157 and the situation was opposite for auxin pathway genes. Precision analysis in psTarget server database identified up-regulation of MIR2877 and MIR530-5p having Os11t0141000-02 and Os07t0239400-01 (PP2A regulatory subunit-like protein and ethylene-responsive small GTP-binding proteins) and MIR396h having Os01t0643300-02 (an auxin efflux carrier protein) and Os01t0643300-01 (a PIN1-like auxin transport protein), as targets with highest probability at anthesis and 5 days after anthesis respectively, in the inferior spikelet and the fold change values of DGE matched with pattern of gene expression (relative transcript level) in the qRT-PCR studies conducted for relevant miRNAs and protein factors for ethylene and auxin signalling. In conclusion, epigenetic regulation of both auxin and ethylene homeostasis control grain filling of rice spikelet was established, but evidences were more robust for the latter.

Summary Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is endemic in some ethnic groups. The association of NPC with the Epstein-Barr virus (EBV) is firmly established; however, the mechanism is still unclear. TLR9 is well known for its essential role in viral pathogen recognition and activation of innate immunity. Here, we report a set of TLR9 polymorphisms in the TIR-2 domain of the TLR9 protein collected from the EBV-infected NPC samples from northeast Indian populations sharing the aforesaid ethnicity. The occurrence of mutations is significantly high in these samples as we found a p value of, Graphical Abstract, Highlights • EBV-associated nasopharyngeal carcinoma (NPC) is endemic in Mongoloids • TLR9 is essential for virus recognition and immunity against cancers • Polymorphisms are common in TLR9 protein in EBV-infected Mongoloids with NPC • NPC susceptibility prediction by TLR9 mutation screening in people for prevention, Biological Sciences; Human Genetics; Cancer

Background Interleukin-28B (IL28B) locus on a human chromosomal region mapped to 19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV) infection the IL28B has a promising role in deciding the consequence of infection for spontaneous clearance of viruses or causing chronic liver infection. Treatment of chronic hepatitis C includes use of direct acting antivirals, Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. Also, interferon free regimens are suggested to be useful in resistant patients. Numerous reports including Genome-Wide Association Studies (GWAS), comprehensive meta-analysis and independent case-control studies in different population have revealed the association between certain Il-28B polymorphisms and response to the PEGIFN- RBV therapy in patients infected with HCV. Method We searched all peer-reviewed relevant and recent literature manually for the present review. Conclusion The GWAS studies have revealed an important role of IL28B in HCV infection, which was supported by many independent studies and meta-analysis by different groups in different ethnicities. IL28B genotyping may be use as predictors of response for IFN-based therapy and personalized treatment of hepatitis C patient.

Kaposi’s sarcoma associated herpesvirus (KSHV) a gammaherpesvirus establishes perennial latency in the host with periodic reactivation. Occasionally change in the physiological condition like hypoxia, host cell differentiation can trigger the lytic switch and reactivation of the virus. The biologically active form of 1, 25(OH)2 D3 plays a critical role in the regulation of various physiological processes (e.g. regulation of mineral homeostasis and control of bone metabolism). Apart from its role in host physiology, 1, 25(OH)2 D3 has been implicated as a potential agent for the prevention and/or treatment of many a tumors. Here we show that 1, 25(OH)2 D3 induces both death of Kaposi sarcoma associated herpesvirus infected PEL cells and KSHV replication. 1, 25(OH)2 D3 mediated inhibition of proliferation was associated with apoptosis of the PEL cells, and virus reactivation. In addition, p38 signalling is required for KSHV reactivation. Furthermore, treatment of PEL cells with p38 inhibitor abrogated the expression of ORF57, thus blocking lytic switch. Furthermore, silencing of VDR resulted in reduced ORF57 expression compared to the control cells, signifying the potential role of 1, 25(OH)2 D3 in KSHV reactivation. Thus, our studies have revealed a novel role of 1, 25(OH)2 D3 in the regulation of KSHV reactivation and PEL cell death.

Kaposi's sarcoma associated herpes virus (KSHV) infected primary effusion lymphoma (PEL) is a rare aggressive form of non-Hodgkin's lymphoma of B cells. KSHV latent and lytic antigens modulate several host cellular signalling pathways especially mammalian target of rapamycin (mTOR), STAT-3 and nuclear factor-kappa B (NF-κB) for rapid tumor progression and immune evasion. Current chemotherapeutic strategies are becoming ineffective as they kill only dividing cells and inefficient to target molecular pathways crucial for active virus replication and its survival. In this study, we evaluated the efficacy of everolimus, an mTOR inhibitor in inducing apoptosis of PEL cells. Dose-dependent treatment of everolimus triggered mitochondria-mediated caspase-dependent apoptosis in PEL cells. Everolimus downregulated KSHV latent antigen expression with concurrent blocking of lytic reactivation for active virus replication. Everolimus also inhibited latent antigen mediated constitutively active STAT-3 and NF-κB signalling. We co-cultured everolimus treated PEL cells with immature dendritic cells and found activation of dendritic cells with increase in surface expression of CD86 and HLA-DR. As everolimus targets and disrupts KSHV antigens as well as antigen facilitated multiple signalling pathways necessary for KSHV survival and maintenance of infection with synchronised boosting of immune system against viral infection, it can be a better therapeutic approach towards treatment of PEL.

Background Non-dividing cells of the myeloid lineage such as monocytes and macrophages are target cells of HIV that have low dNTP pool concentrations and elevated levels of dUTP, which leads to frequent incorporation of dUMP opposite to A during reverse transcription (“uracilation”). One factor determining the fate of dUMP in proviral DNA is the host cell uracil base excision repair (UBER) system. Here we explore the relative UBER capacity of monocytes (MC) and monocyte-derived macrophages (MDM) and the fate of integrated uracilated viruses in both cell types to understand the implications of viral dUMP on HIV diversification and infectivity.Results We find that monocytes are almost completely devoid of functional UBER, while macrophages are mainly deficient in the initial enzyme uracil DNA glycosylase (hUNG2). Accordingly, dUMP persists in viral DNA during the lifetime of a MC and can only be removed after differentiation of MC into MDM. Overexpression of human uracil DNA glycosylase in MDM prior to infection resulted in rapid removal of dUMP from HIV cDNA and near complete depletion of dUMP-containing viral copies. This finding establishes that the low hUNG2 expression level in these cells limits UBER but that hUNG2 is restrictive against uracilated viruses. In contrast, overexpression of hUNG2 after viral integration did not accelerate the excision of uracils, suggesting that they may poorly accessible in the context of chromatin. We found that viral DNA molecules with incorporated dUMP contained unique (+) strand transversion mutations that were not observed when dUMP was absent (G→T, T→A, T→G, A→C). These observations and other considerations suggest that dUMP introduces errors predominantly during (-) strand synthesis when the template is RNA. These mutations may arise from the increased mispairing and duplex destabilizing effects of dUMP relative to dTMP during reverse transcription. Overall, the likelihood of producing a functional virus from in vitro infection of MC is about 50-fold and 300-fold reduced as compared to MDM and activated T cells.Conclusions The results implicate viral dUMP incorporation in MC and MDM as a potential viral diversification and restriction pathway during human HIV infection.

Nasopharyngeal carcinoma (NPC) is one the most confusing and rare malignancy in most part of the world with significantly high occurrence in some populations of Southeast Asia, North Africa and Alaska. Apart from the dietary and environmental factors, NPC is well-associated with Epstein-Barr virus (EBV) infection in these ethnic groups. However, the internal molecular mechanism(s) for such association in specific populations is not known till date. Polymorphisms in the genes of histocompatibility locus antigens (HLA) are reported in NPC, but association of any particular polymorphism with ethnicity is not established yet. Here, we report a set of HLA polymorphisms in EBV-infected NPC samples from Northeast Indian population. These polymorphisms might play an important role for the lack of proper immune function against EBV infection and thus, eventually, for NPC generation in endemic populations like those of Northeast India.

Cancer is one of the major threat to human society, which is the second leading global cause of mortality after cardiovascular diseases. Most popular chemo-therapy and radiation-therapy have a significant impact on cancer treatment but till date, they are not successful in many advanced cases and metastatic stage of cancer. This leads the researcher to investigate new strategies to combat by selectively killing cancer cells without damaging normal cells. Viral oncotherapy is such a hopeful treatment option that offers an opportunity for targeting cancer cells. In this therapy, wild type or engineered oncolytic viruses are use to infect and destroy cancer cells by oncolysis. As a result of this new infectious viral particles are release to facilitate the destruction of the remaining cancerous cells. These viruses with anticancer activity can be designed in many ways and use in combination with other cancer therapy to increase their tumor selectivity and improve oncolytic activity. Here, we will discuss the strategies for oncolytic viral engineering with the mechanisms by which these viruses specifically kill tumor cells that make a promising modality for cancer therapy.

The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C.

Studies have suggested that Epithelial–Mesenchymal Transition (EMT) and transformation is an important step in progression to cancer. Par3 (partitioning-defective protein) is a crucial factor in regulating epithelial cell polarity. However, the mechanism by which the latency associated nuclear antigen (LANA) encoded by Kaposi's Sarcoma associated herpesvirus (KSHV) regulates Par3 and EMTs markers (Epithelial-Mesenchymal Transition) during viral-mediated B-cell oncogenesis has not been fully explored. Moreover, several studies have demonstrated a crucial role for EMT markers during B-cell malignancies. In this study, we demonstrate that Par3 is significantly up-regulated in KSHV-infected primary B-cells. Further, Par3 interacted with LANA in KSHV positive and LANA expressing cells which led to translocation of Par3 from the cell periphery to a predominantly nuclear signal. Par3 knockdown led to reduced cell proliferation and increased apoptotic induction. Levels of SNAIL was elevated, and E-cadherin was reduced in the presence of LANA or Par3. Interestingly, KSHV infection in primary B-cells led to enhancement of SNAIL and down-regulation of E-cadherin in a temporal manner. Importantly, knockdown of SNAIL, a major EMT regulator, in KSHV cells resulted in reduced expression of LANA, Par3, and enhanced E-cadherin. Also, SNAIL bound to the promoter region of p21 and can regulate its activity. Further a SNAIL inhibitor diminished NF-kB signaling through upregulation of Caspase3 in KSHV positive cells in vitro. This was also supported by upregulation of SNAIL and Par3 in BC-3 transplanted NOD-SCID mice which has potential as a therapeutic target for KSHV-associated B-cell lymphomas., Author Summary Par3 (partitioning-defective protein) is characterized as a cell polarity protein with a crucial role in regulating EMT progression in KSHV-infected cells. Notably, SNAIL, a major EMT regulator is targeted through expression of Par3 and Latency associated nuclear antigen (LANA) during KSHV infection. In this study we show that LANA positively regulated Par3 and SNAIL while E-cadherin was inversely regulated during KSHV infection of B-cells. Furthermore, SNAIL binding with the potent kinase inhibitor p21 in KSHV positive cells enhanced NF-kB signaling. These results demonstrate the importance of Par3 and SNAIL in development of KSHV-induced B-cells cancers through regulation of EMT related antigens, and may be critical for driving KSHV-associated primary effusion lymphoma.

Kaposi’s sarcoma-associated herpesvirus (KSHV) infects a variety of human cells including cells of epithelial, mesenchymal and endothelial origin. The latency associated nuclear antigen (LANA) of this virus regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. TAp63α can induce apoptosis in stressed cells by upregulating various death receptors and loss of mitochondrial membrane potential. The present study demonstrates that LANA inhibits TAp63α-mediated apoptosis by a direct interaction with each other. This interaction also results in a reduction in loss of mitochondrial membrane potential caused by TAp63α. Therefore the present study indicates a possible mechanism of KSHV-infected cells to escape apoptosis and facilitate survival.

The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA) plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole) induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case–control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy–Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.