Human Papillomavirus 16 DNA Methylation Patterns and Investigation of Integration Status in Head and Neck Cancer Cases.

Persistent high-risk human papillomavirus (HPV) infection is a pivotal factor in the progression of cervical cancer. In recent years, an increasing interest has emerged in comprehending the influence of HPV on head and neck squamous cell carcinoma (HNSCC). Notably, it is well established that HPV-associated HNSCC show cases with distinct molecular and clinical attributes compared to HPV-negative cases. The present study delves into the epigenetic landscape of HPV16, specifically its L1 gene and untranslated region (UTR), through pyrosequencing, while the HPV16 DNA physical status was evaluated using E2/E6 ratio analysis in HPV16-positive HNSCC FFPE biopsies. Our findings reveal substantial methylation across six sites within the HPV16 L1 gene and seven sites in the UTR. Specifically, methylation percentages of two L1 CpG sites (7136, 7145) exhibit significant associations with tumor histological grade (p < 0.01), while proving concurrent methylation across multiple sites. The HPV16 DNA physical status was not correlated with the methylation of viral genome or tumor characteristics. This is the first study that examines epigenetic modifications and the HPV16 DNA physical status in Greek HNSCC patients. Our findings suggest an orchestrated epigenetic modulation among specific sites, impacting viral gene expression and intricate virus-host interactions.

Th17 serum cytokines in relation to laboratory-confirmed respiratory viral infection: A pilot study.

BACKGROUND: Th17 cytokines are associated with modulation of inflammation and may be beneficial in clearing influenza infection in experimental models. The Th17 cytokine profile was evaluated in a pilot study of respiratory virus infections. METHODS: Consecutive patients with symptoms of respiratory tract infection visiting the emergency department of a tertiary care hospital during the winter influenza season of 2014 to 2015 were evaluated. CLART PneumoVir kit, (GENOMICA, Madrid, Spain) was used for viral detection of all known respiratory viruses. Th17 cytokine profile was evaluated with the MILLIPLEX MAP Human TH17 Magnetic Bead Panel (Millipore Corp., Billerica, MA). Correlation of the TH17 profile with viral detection was performed with univariate and multivariate analysis. RESULTS: Seventy-six patients were evaluated (median age 56 years, 51.3% female); a respiratory virus was identified in 60 (78.9%) patients; 45% had confirmed influenza. Influenza A (H3N2) correlated with higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1ß (IL-1ß), IL-17A, IL-17E, IL-17F, IL-21, IL-22, and IL-23 (P < 0.05 by analysis of variance [ANOVA]) compared with respiratory syncytial virus (RSV). Parainfluenza virus (PIV) similarly had higher levels of GM-CSF, IL-1b, IL-17A, IL-22 compared with those detected in RSV, influenza B and any other virus infection ( P < 0.05; ANOVA). Increasing age (ß-coefficient = 1.11, 95% CI, 1.04-1.2, P < 0.01) as well as IL-17A levels (ß-coefficient = 1.03, 95% CI, 1.001-1.05, P = 0.04) predicted hospital admission. CONCLUSION: Main Th17 cell effector cytokines were upregulated in laboratory-confirmed A(H3N2) influenza and PIV. Excessive amounts of Th17 cytokines may be implicated in the pathogenesis and immune control of acute influenza and PIV infection in humans and may predict the severity of disease.

A prospective study on the epidemiology and clinical significance of viral respiratory infections among pediatric oncology patients.

Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART® PneumoVir kit (GENOMICA, Spain). Α detailed questionnaire including demographics and medical history was also completed. Samples were processed in batches, results were communicated as soon as they became available. Children recruited in whom no virus was detected composed the no virus detected group. Viral prevalence was 38.4% in children presenting with respiratory illness. A single virus was found in 30.4%, with RSV being the most frequent. Viral coinfections were detected in 8%. Children with viral infection were more likely to be febrile upon enrollment and to present with lower respiratory signs/symptoms. They had longer duration of illness and they were more likely to receive antibiotics/antifungals. Only 22% of children with influenza received oseltamivir. Mortality was low (2.7%), however, pediatric intensive care unit (PICU) admission and death were correlated with virus detection. In our study mortality was low and PICU admission was related to virus identification. Further research is needed to clarify whether antibiotics in virus-proven infection are of value and underline the importance of oseltamivir's timely administration in influenza.

Association of p16 (CDKN2A) polymorphisms with the development of HPV16-related precancerous lesions and cervical cancer in the Greek population.

The tumor suppressor protein p16 plays a fundamental role in cell cycle regulation and exerts a protective effect against tumor growth. Two different polymorphisms at positions 540 and 580 at the 3'UTR of exon 3 of p16 gene are implicated in several types of cancer, while their role in cervical cancer development remains rather vague. In the present study, we investigated for the impact of p16 genotypes/haplotypes on patients' vulnerability to cervical disease and examined whether these factors can be used as progression markers in the Greek population. A total of 96 HPV16 positive samples and histologically confirmed as LSIL (42 samples), HSIL (44 samples), and cervical cancer cases (10 samples) along with 50 control cases were tested. The identification of p16 polymorphisms was performed by PCR-RFLP methodology. The present analysis revealed that women with p16 540 CG/GG genotype are at a 2.7-fold higher risk of developing HPV16-associated HSIL (OR = 2.7, 95%CI: 1.01-6.6, P = 0.028). The G allele can be regarded as a risk factor of developing HSIL in the Greek population (OR = 2.7, 95%CI: 1.2-5.9, P = 0.012). Moreover, p16 polymorphism C580T is not associated with the growth of cervical lesion in Greek patients, while 540G/580C haplotype can be regarded as a risk haplotype of developing HSIL (OR = 3.67, 95%CI: 1.56-8.6, P = 0.0019). Our results demonstrated that p16 C540G polymorphism influence patients' susceptibility to more severe dysplasia and consequently this polymorphism could potentially emerge as a valuable biomarker for HSIL development in the Greek population.

Mixed viral infections of the respiratory tract; an epidemiological study during consecutive winter seasons.

The current study aimed to describe the molecular epidemiology of mixed respiratory viral infections during consecutive winter seasons in a tertiary care hospital. Patients with symptoms of respiratory tract infection were evaluated during the 2009-2011 and 2013-15 winter seasons. A clinical microarray technique was used for viral detection. Clinical and epidemiological data were correlated with mixed viral detection and the need for hospitalization. In 332 out of 604 (54.4%) evaluated patients (17.6% children) a respiratory virus was identified. Mixed viral infections were diagnosed in 68/332 (20.5%) patients with virus detection (66.2% mixed Influenza-RSV infections). Mixed viral infections were more commonly detected in children (OR 3.7; 95%CI 1.9-5.6, P < 0.01) and patients with comorbidities. In logistic regression analyses, mixed viral infections were associated with younger age (mean age 30.4 years vs. 41.8 years, P ≤ 0.001) and increased rates of fever (OR: 2.7; 95%CI 1.04-7.2, P < 0.05) but no adverse outcomes or increased rates of hospitalization. High rates of mixed viral infections were noted during all winter seasons (especially Influenza and RSV) and were more common in younger patients. The clinical significance of mixed respiratory viral infection needs further elucidation.

Comparison between Nageotte and flow cytometric counting of residual leucocytes in freshly prepared leucocyte-reduced red blood cell components.

BACKGROUND: Flow cytometry (FC) and Nageotte hemocytometry represent the most widely accepted methods for counting residual white blood cells (rWBCs) in leucocyte-reduced (LR) blood components. Our aim was to study the agreement between the two methods, under real working blood bank conditions. MATERIALS AND METHODS: 94 freshly produced LR red blood cell (RBC) units were tested for rWBC concentrations by FC and Nageotte. To assess the precision of each method, we calculated the intra-assay coefficients of variation (CV), and followed the Bland-Altman methodology to study the agreement between the two methods. RESULTS: CV was 18.5% and 26.2% for the Nageotte and the FC, respectively. However, the agreement between the duplicate observations, using the binary cut-off threshold of 1 × 106 WBCs per unit to define the results as "pass/fail", was 71.9% for the Nageotte and 93.3% for the FC. Linear regression analysis did not show any correlation (R-squared = 0.01, p = 0.35) between the two methods, while the Bland-Altman analysis for the measuring agreement showed a bias toward a higher Nageotte count of 0.77 × 106 leucocytes per unit (p < 0.001) with the 95% limits of agreement (d ± 2 sd) ranging from -0.40 × 106 to 1.94 × 106 leucocytes per unit. CONCLUSION: The absence of agreement between Nageotte and FC method, with the differences within d ± 2 sd being of high clinical importance, suggests that the two methods cannot be used for clinical purposes interchangeably. The Nageotte seems unsuitable for quality control even with a pass-fail criterion, under real working blood bank conditions.

Quantitative Measurement of L1 Human Papillomavirus Type 16 Methylation for the Prediction of Preinvasive and Invasive Cervical Disease.

Background: Methylation of the human papillomavirus (HPV) DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within the L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV16 genotype. Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results: We found that the L1 HPV16 mean methylation (±SD) significantly increased with disease severity (cervical intraepithelial neoplasia [CIN] 3, 17.9% [±7.2] vs CIN2, 11.6% [±6.5], P < .001 or vs CIN1, 9.0% [±3.5], P < .001). Mean methylation was a good predictor of CIN3+ cases; the area under the curve was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+ showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively) and positive and negative predictive values (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%. Conclusions: Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16-positive women that have high-grade disease or worse.

HPV16 E6 Oncogene Contributes to Cancer Immune Evasion by Regulating PD-L1 Expression through a miR-143/HIF-1a Pathway.

Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these viruses' oncogenes E6 and E7 into the host's genome affects a multitude of cellular functions and alters the expression of molecules. The aim of this study was to investigate how these oncogenes contribute to the expression of immune system control molecules, using cell lines with integrated HPV16 genome, before and after knocking out E6 viral gene using the CRISPR/Cas9 system, delivered with a lentiviral vector. The molecules studied are the T-cell inactivating protein PD-L1, its transcription factor HIF-1a and the latter's negative regulator, miR-143. According to our results, in the E6 knock out (E6KO) cell lines an increased expression of miR-143 was recorded, while a decrease in the expression of HIF-1a and PD-L1 was exhibited. These findings indicate that E6 protein probably plays a significant role in enabling cervical cancer cells to evade the immune system, while we propose a molecular pathway in cervical cancer, where PD-L1's expression is regulated by E6 protein through a miR-143/HIF-1a axis.

Expression profile of miRNAs computationally predicted to target PDL-1 in cervical tissues of different histology groups.

Background: Human papilloma virus (HPV) is considered a successful pathogen as it has the ability to evade host immune responses and establish long-term persistent infection. It has been reported that programmed death ligand 1 (PDL-1) expression is correlated with HPV-positivity and is increased with lesion progression or tumor metastasis in cervical cancer. The expression of microRNAs (miRNAs) is often deregulated in cancer, and their potential targets are affected. Methods: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) cervical samples of different histological types, previously typed for the presence of HPV. A specific quantitative polymerase chain reaction (qPCR) protocol with SYBR Green was used to check for the expression of four miRNAs that were computationally predicted to target PDL-1. Results and conclusion: hsa-miR-20a-5p and hsa-miR-106b-5p showed an expression increase with the severity of the lesions, while hsa-miR-125b-5p depicted a significant decrease in its expression in cancerous samples when compared to normal samples.

Exploration of Methodologies for Developing Antimicrobial Fused Filament Fabrication Parts.

Composite 3D printing filaments integrating antimicrobial nanoparticles offer inherent microbial resistance, mitigating contamination and infections. Developing antimicrobial 3D-printed plastics is crucial for tailoring medical solutions, such as implants, and cutting costs when compared with metal options. Furthermore, hospital sustainability can be enhanced via on-demand 3D printing of medical tools. A PLA-based filament incorporating 5% TiO2 nanoparticles and 2% Joncryl as a chain extender was formulated to offer antimicrobial properties. Comparative analysis encompassed PLA 2% Joncryl filament and a TiO2 coating for 3D-printed specimens, evaluating mechanical and thermal properties, as well as wettability and antimicrobial characteristics. The antibacterial capability of the filaments was explored after 3D printing against Gram-positive Staphylococcus aureus (S. aureus, ATCC 25923), as well as Gram-negative Escherichia coli (E. coli, ATCC 25922), and the filaments with 5 wt.% embedded TiO2 were found to reduce the viability of both bacteria. This research aims to provide the optimal approach for antimicrobial and medical 3D printing outcomes.

Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings-A Molecular Epidemiology Study.

Prevalent cervical HPV infection and high-risk HPV persistence consequences have been extensively investigated in the literature; nevertheless, any causative interrelations of other sexually transmitted bacterial infections (STIs) with cervical HPV infection have not yet been fully elucidated. This study aimed to investigate the possible association of STIs with cervical cytology aberrations and HPV genotyping results in a representative sample of predominantly young Greek women. Liquid-based cytology and molecular detection for bacterial STIs and HPV as well as extended HPV genotyping were simultaneously assessed in cervical samples from 2256 individuals visiting several urban outpatient Gynecology Departments for well-woman visits or cervical screening throughout a 20-month period. All specimens were centrally processed with validated molecular assays. The mean age of the studied women was 37.0 ± 11.7 years; 722 women (33.30%) tested positive for STI (mean age 34.23 ± 10.87 years). A higher mean age (38.34 ± 11.83 years (p < 0.05)) was associated with negative STI testing. Chlamydia trachomatis was detected in 59 individuals (8.2%), Mycoplasma hominis in 156 (21.6%), Mycoplasma genitalium in 14 (1.9%), and Ureaplasma spp. in 555 (76.9%); infections with two bacterial pathogens were identified in 73 samples (10.1%). Cervical HPV was detected in 357 out of 1385 samples with a valid HPV typing result (25.8%). The mean age of HPV-positive women was 32.0 ± 8.4 years; individuals testing HPV-negative were slightly older (N = 1028): 34.4 ± 9.2 (p < 0.05). Among the 1371 individuals with valid results both for bacterial STIs and cervical HPV detection, women with an HPV-positive sample were more likely to harbor an STI (OR: 2.69, 95% CI 2.10-3.46, p < 0.05). Interestingly, bacterial STI positivity illustrated significant heterogeneity between NILM and LSIL cases, with 28.88% of NILM and 46.33% of LSIL cases harboring an STI, respectively (p < 0.05). In brief, in a population with a high prevalence for STIs, especially Ureaplasma spp., an association was documented between bacterial pathogen detection and cervical HPV infection, as well as abnormal cytology; these findings merit further investigation.

Identification of women for referral to colposcopy by neural networks: a preliminary study based on LBC and molecular biomarkers.

Objective of this study is to investigate the potential of the learning vector quantizer neural network (LVQ-NN) classifier on various diagnostic variables used in the modern cytopathology laboratory and to build an algorithm that may facilitate the classification of individual cases. From all women included in the study, a liquid-based cytology sample was obtained; this was tested via HPV DNA test, E6/E7 HPV mRNA test, and p16 immunostaining. The data were classified by the LVQ-NN into two groups: CIN-2 or worse and CIN-1 or less. Half of the cases were used to train the LVQ-NN; the remaining cases (test set) were used for validation. Out of the 1258 cases, cytology identified correctly 72.90% of the CIN-2 or worst cases and 97.37% of the CIN-1 or less cases, with overall accuracy 94.36%. The application of the LVQ-NN on the test set allowed correct classification for 84.62% of the cases with CIN-2 or worse and 97.64% of the cases with CIN-1 or less, with overall accuracy of 96.03%. The use of the LVQ-NN with cytology and the proposed biomarkers improves significantly the correct classification of cervical precancerous lesions and/or cancer and may facilitate diagnosis and patient management.

Evaluation of the role of the new INNOVANCE PFA P2Y test cartridge in detection of clopidogrel resistance.

Light transmittance aggregometry (LTA) has been extensively used in monitoring clopidogrel therapy. However, the availability of simple and rapid point-of-care platelet function assays is of great clinical importance. Thus, the manufacturer of the Platelet Function Analyzer (PFA)-100 System has recently produced the INNOVANCE PFA P2Y test cartridge. We assessed the ability of this new test to reliably detect clopidogrel resistance. We enrolled 90 consecutive patients with coronary artery disease receiving chronic clopidogrel maintenance therapy in combination with aspirin. Twenty healthy volunteers served as controls. Clopidogrel resistance was simultaneously analysed by the INNOVANCE PFA P2Y test cartridge, ADP-induced LTA, the flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and the multiple electrode aggregometry (Multiplate). Agreement among the four platelet function methods by two was assessed using Cohen's kappa coefficient. According to the cut-off points for clopidogrel resistance proposed by the literature, agreement was fair between INNOVANCE PFA-100 P2Y and LTA (74.4%) and Multiplate (75.6%), while poor agreement was noticed in VASP assay (63.3%). Based on cut-off points indicating a higher thrombotic risk, agreement between the PFA-100 System and the other three methods did not significantly differ compared to the previous cut-offs (72.2%, 71.1% and 55.1%, respectively). The INNOVANCE PFA-100 P2Y test seems to be comparable to other established platelet function assays in detecting clopidogrel resistance. However, the modest agreement among platelet function methods makes the performance of platelet function testing crucial with more than one technique in order to reliably identify poor responders to clopidogrel treatment.

Genetic variability and phylogeny of high risk HPV type 16, 18, 31, 33 and 45 L1 gene in Greek women.

The present study explores nucleotide variability, phylogeny and association with cervical neoplasia in high risk HPV types 16, 18, 31, 33 and 45 collected from Greek women. Of the 1894 women undergoing routine cervical cytology examination, 160 samples test positive for single infections of HPV type 16 (n = 104), HPV 31 (n = 40), HPV 33 (n = 7), HPV 18 (n = 5), and HPV 45 (n = 4) were typed by microarrays method, amplified by PCR then sequenced and phylogenetically analyzed. For HPV 16, 9 variants with nucleotide variations were included into the study. For HPV 31, 33, 18 and 45, nucleotide variations were identified in 6, 4, 2 and 3 variants, respectively. The Bayesian inference and Maximum Parsimony methods were used in order to construct the phylogenetic trees. When types were analyzed independently HPV 16 (European and non-European) and HPV 18 (African and non-African) formed distinct clades. The genomic characterization of HPV variants will be important for illuminating the geographical relatedness and biological differences and for the determination of their risk.

West Nile Disease Symptoms and Comorbidities: A Systematic Review and Analysis of Cases.

West Nile virus (WNV) is a mosquito-borne flavivirus that has emerged as a major cause of viral encephalitis and meningitis, rarely leading to death. Several risk factors have been discussed in the past concerning the severity of the disease, while few reports have focused on precipitating conditions that determine of WNV-related death. Studies on cohorts of patients suffering of West Nile disease (WND) usually encompass low numbers of deceased patients as a result of the rarity of the event. In this systematic review and critical analysis of 428 published case studies and case series, we sought to evaluate and highlight critical parameters of WND-related death. We summarized the symptoms, comorbidities, and treatment strategies related to WND in all published cases of patients that included clinical features. Symptoms such as altered mental status and renal problems presented increased incidence among deceased patients, while these patients presented increased cerebrospinal fluid (CSF) glucose. Our analysis also highlights underestimated comorbidities such as pulmonary disease to act as precipitating conditions in WND, as they were significantly increased amongst deceased patients. CSF glucose and the role of pulmonary diseases need to be revaluated either retrospectively or prospectively in WND patient cohorts, as they may be linked to increased mortality risk.

Mutation Profile of HPV16 L1 and L2 Genes in Different Geographic Areas.

The causal relationship between HPV and cervical cancer in association with the high prevalence of high risk HPV genotypes led to the design of HPV vaccines based on the major capsid L1 protein. In recent years, capsid protein L2 has also become a focal point in the field of vaccine research. The present review focuses on the variability of HPV16 L1 and L2 genes, emphasizing the distribution of specific amino acid changes in the epitopes of capsid proteins. Moreover, a substantial bioinformatics analysis was conducted to describe the worldwide distribution of amino acid substitutions throughout HPV16 L1, L2 proteins. Five amino acid changes (T176N, N181T; EF loop), (T266A; FG loop), (T353P, T389S; HI loop) are frequently observed in the L1 hypervariable surface loops, while two amino acid substitutions (D43E, S122P) are adjacent to L2 specific epitopes. These changes have a high prevalence in certain geographic regions. The present review suggests that the extensive analysis of the amino acid substitutions in the HPV16 L1 immunodominant loops may provide insights concerning the ability of the virus in evading host immune response in certain populations. The genetic variability of the HPV16 L1 and L2 epitopes should be extensively analyzed in a given population.

The T350G Variation of Human Papillomavirus 16 E6 Gene Prevails in Oropharyngeal Cancer from a Small Cohort of Greek Patients.

Recent trends have shown a dramatic rise in the incidence of oropharyngeal squamous cell carcinoma strongly associated with high-risk human papillomavirus (HPV) of type 16. The genetic variability of HPV16 has been extensively studied in cervical cancer but there are very limited published data concerning the genetic variations of this HPV type in oropharyngeal cancer. In the present study, the genetic variations of HPV16 E6 gene sequences originated from a small cohort of Greek patients diagnosed with oropharyngeal cancer were assessed. The vast majority of the sequences clustered within the European variant branch. The T350G variation was found to be the predominant one. This finding may indicate the need for further studies that could explain the possible impact of this variant in the pathomechanisms of oropharyngeal cancer.

Performance evaluation of manual and automated (MagNA pure) nucleic acid isolation in HPV detection and genotyping using Roche Linear Array HPV Test.

Nucleic acids of human papillomavirus (HPV) isolated by manual extraction method (AmpliLute) and automated MagNA pure system were compared and evaluated with cytohistological findings in 253 women. The concordance level between AmpliLute and MagNA was very good 93.3% (κ = 0.864, P < .0001). Overall HPVpositivity detected by AmpliLute was 57.3% (30.4% as single and 27% as multiple infections) in contrast to MagNA 54.5% (32% and 23%, resp.). Discrepant results observed in 25 cases: 11 MagNA(-)/AmpliLute(+), 10 of which had positive histology; 5 MagNA(+)/AmpliLute(-) with negative histology; 8 MagNA(+)/AmpliLute(+): in 7 of which AmpliLute detected extra HPV genotypes and 1 MagNA(invalid)/AmpliLute(+) with positive histology. Both methods performed well when compared against cytological (area under curve (AUC) of AmpliLute 0.712 versus 0.672 of MagNA) and histological diagnoses (AUC of AmpliLute 0.935 versus 0.877 of MagNA), with AmpliLute showing a slightly predominance over MagNA. However, higher sensitivities, specificities, and positive/negative predictive values were obtained by AmpliLute.

Animal Coronaviruses Induced Apoptosis.

Apoptosis is a form of programmed death that has also been observed in cells infected by several viruses. It is considered one of the most critical innate immune mechanisms that limits pathogen proliferation and propagation before the initiation of the adaptive immune response. Recent studies investigating the cellular responses to SARS-CoV and SARS-CoV-2 infection have revealed that coronaviruses can alter cellular homeostasis and promote cell death, providing evidence that the modulation of apoptotic pathways is important for viral replication and propagation. Despite the genetic diversity among different coronavirus clades and the infection of different cell types and several hosts, research studies in animal coronaviruses indicate that apoptosis in host cells is induced by common molecular mechanisms and apoptotic pathways. We summarize and critically review current knowledge on the molecular aspects of cell-death regulation during animal coronaviruses infection and the viral-host interactions to this process. Future research is expected to lead to a better understanding of the regulation of cell death during coronavirus infection. Moreover, investigating the role of viral proteins in this process will help us to identify novel antiviral targets related to apoptotic signaling pathways.