Viral Factors Research Articles

Role of hepatotropic viruses in promoting hepatocellular carcinoma-current knowledge and recent advances.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with chronic infections by hepatotropic viruses such as hepatitis B virus (HBV), and hepatitis C virus (HCV), being major risk factors. Chronic infections with these viruses are the leading cause of HCC worldwide, with HBV alone responsible for over 50% of cases. Despite advances in direct-acting antivirals (DAAs) for HCV and nucleos(t)ide analogues (NAs) for HBV, challenges remain in HCC prevention, early detection, and treatment. Recent research highlights the role of viral-induced metabolic alterations, such as the Warburg effect, mitochondrial dysfunction, and lipid dysregulation, in promoting HCC. Moreover, immune checkpoint inhibitors have emerged as effective treatments for advanced HCC, though responses vary between HBV- and HCV-related cancers. Additionally, novel therapeutic approaches and metabolic-targeted therapies offer promising avenues for virus-associated HCC treatment. Advancements in liquid biopsy biomarkers and artificial intelligence-driven diagnostics are improving HCC surveillance and risk stratification, potentially enabling earlier interventions. While HBV vaccination has significantly reduced HCC incidence, disparities in global vaccination coverage persist. Furthermore, antiviral therapies combined with structured surveillance programs have proven effective in reducing HCC incidence and mortality. This review highlights the complex connection between viral, genetic, and environmental factors in HCC development and underscores the importance of integrated prevention strategies to reduce its burden globally.

The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques

Congenital cytomegalovirus (cCMV) is the leading infectious cause of neonatal neurological impairment worldwide, but the viral factors enabling vertical spread across the placenta remain undetermined. The pentameric complex (PC), composed of the subunits gH/gL/UL128/UL130/UL131A, has been demonstrated to be important for entry into nonfibroblast cells in vitro. These findings link the PC to broad cell tropism and virus dissemination in vivo, denoting all subunits as potential targets for intervention strategies and vaccine development. To determine the relevance of the PC for congenital transmission in a translational nonhuman primate model, we engineered a rhesus CMV (RhCMV) mutant lacking the orthologs of UL128 and UL130, which demonstrated diminished infection of epithelial cells in vitro. However, intravenous inoculation of either CD4 + T cell–depleted or immunocompetent RhCMV-seronegative pregnant rhesus macaques (RMs) in the early second trimester with the PC-deficient mutant resulted in maternal RhCMV peak plasma viremia similar to inoculations with PC-intact RhCMV, although virus shedding in saliva and urine was limited. Infections with the PC-intact virus induced IgG responses that neutralized RhCMV entry into epithelial cells in tissue culture. These responses were reduced, but not absent, from animals infected with the PC-deficient virus, which also induced IgG responses against gH. Moreover, congenital CMV transmission was confirmed in multiple animals infected with PC-deficient virus by detecting viral DNA in the amniotic fluid, indicating that transplacental transmission in RMs is not contingent on the PC.

Role of human herpesvirus homologs of infected cell protein 27 (ICP27) in the biogenesis, processing, and maturation of mRNAs.

Herpesviruses are enveloped viruses with large double-stranded DNA genomes that are highly prevalent in the human population and elicit numerous types of clinical manifestations, from mild to severe. These viruses are classified into three subfamilies: alpha-, beta-, and gammaherpesvirinae, all capable of establishing life-long persistent infections in the host. As strict intracellular parasites, these viruses have evolved molecular determinants to support and modulate viral and host gene transcription processes during infection and the translation of messenger RNAs (mRNAs) to synthesize proteins that participate in cellular pathways promoting their replication cycles and virion formation. Notably, some of these proteins have functional RNA-binding domains consisting of arginine-glycine-glycine (RGG) amino acid (aa) sequences that, when methylated, regulate their nucleic acid-binding capacities and can influence the export of mRNAs lacking introns from the nucleus into the cytoplasm. Additional domains and motifs in these proteins mediate their interactions with regulatory proteins related to RNA splicing, either promoting or repressing mRNA processing. Notably, all human herpesviruses (HHVs) encode in their genomes proteins that share homology with infected cell protein 27 (ICP27) of herpes simplex virus type 1 (HSV-1), which can significantly impact the biogenesis of mRNAs and their processing during infection. Here, we review and discuss the roles of ICP27 and the corresponding homologs encoded in different human herpesviruses, focusing on their similarities and differences in structure and function. A more profound knowledge of the role of key viral factors required for effective herpesvirus replication could aid in the design and identification of novel antivirals to treat the diseases produced by these viruses.

Viral and immune factors associated with COVID-19 outcome in the C3PO trial of convalescent plasma.

We examined innate and antibody responses in C3PO clinical trial participants of COVID-19 convalescent plasma to identify predictors of disease progression. We found SARS-CoV-2 viremia in 64% of participants at enrollment, and we could also quantify viremia in approximately half of those samples using an RT-PCR assay. Viremia was associated with increased risk of disease progression (OR 3.0, 95% CI 1.7-5.0). Participants with viremia at baseline had lower SARS-CoV-2 binding antibody levels and higher pro-inflammatory cytokine levels, including IP-10 (CXCL10), TNF-α, calprotectin, and CRP. Disease progression correlated with extracellular vesicle levels from multiple cell types in the convalescent but not acute phase of the disease. Male sex predicted worse disease outcome and was associated with higher baseline levels of several pro-inflammatory cytokines. Viremia's strong predictive value for disease progression argues for further study of its use to predict which patients with COVID-19 might require more intensive therapy or monitoring.

MicroRNAs in HIV infection: dual regulators of viral replication and host immunity.

MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression by binding to target messenger RNAs (mRNAs), leading to their degradation or translational repression. Over the past few years, significant progress has been made in understanding the role of miRNAs in various biological processes, including viral infections such as human immunodeficiency virus (HIV). HIV infection is characterized by a complex interaction between the virus and the host's immune system, where miRNAs have emerged as key regulators. MiRNAs influence HIV infection by modulating both viral replication and the host immune response. Researchers have identified several host miRNAs that suppress or enhance HIV replication by targeting viral genes or host factors essential for the virus life cycle. Conversely, HIV has evolved mechanisms to manipulate the host's miRNA machinery to its advantage. The virus can downregulate or upregulate specific host miRNAs to create a more favorable environment for replication and persistence. Moreover, HIV infection can alter the expression profiles of various miRNAs in infected cells, which can contribute to immune dysregulation and disease progression. Dysregulation of miRNAs is associated with HIV-associated complications, such as neurocognitive disorders and cardiovascular diseases. Understanding the specific roles of miRNAs in HIV pathogenesis could lead to the development of novel therapeutic strategies, such as miRNA-based therapies, to control HIV infection and its associated comorbidities. Understanding the role of miRNAs in HIV infection reveals their significant influence on the complex interactions between the virus and the host, impacting the course of infection and disease progression. Also, continued research in miRNA-mediated mechanisms in HIV holds the potential for uncovering new insights into viral pathogenesis and developing innovative therapeutic approaches.

Dengue Virus Life Cycle and Host Protein Interactions: Focus on RNA Binding Proteins and Therapeutic Advances.

Dengue, a widespread arthropod-borne viral disease, remains endemic in more than 100 nations, affecting over 40% of the world's population, with millions of cases reported annually, and has a major burden on global public health systems. The causative agent of this infection is the dengue virus which belongs to the Flaviviridae family of RNA viruses. The DENV infection leads to a broad spectrum of clinical symptoms, ranging from mild to severe, and even fatal in the cases of secondary infection. In the absence of promising antiviral therapies or vaccines to effectively combat the infection, understanding the interaction between the host and pathogen, along with the associated molecular mechanisms, is crucial. In this review, we focused on the specialised functions of various RNA-binding proteins (RBPs) and their roles at various stages of the viral life cycle. This review examines the intricate interplay between viral and host cellular factors. Notably, numerous host RBPs, including La, eIF2, PTBP1, YBX1, and other hnRNPs, interact with viral components, such as NS2A, NS2B, NS3, NS4A, NS4B and NS5, and most importantly, the viral UTRs (untranslated regions), to facilitate critical stages of the viral life cycle. We comprehensively compiled the specific roles of RBPs in the dengue virus life cycle, including viral entry, translation, transcription, and assembly, and further explored the therapeutic possibilities.

Porcine reproductive and respiratory syndrome virus nsp5 inhibits the activation of the Nrf2/HO-1 pathway by targeting p62 to antagonize its antiviral activity.

Porcine reproductive and respiratory syndrome virus (PRRSV) infections often trigger oxidative stress and cytokine storms, resulting in significant tissue damage that causes fatalities in piglets and reproductive issues in sows. However, it is still unknown how oxidative stress is regulated by viral and host factors in response to PRRSV infection. Here, we found that PRRSV induced cellular oxidative stress by triggering the production of reactive oxygen species and inhibiting the expression of antioxidant enzymes. Although Nrf2 is an important redox regulator that initiates the expression of downstream antioxidant genes, PRRSV can impair the Nrf2/HO-1 pathway. The overexpression of Nrf2 showed a significant anti-PRRSV effect, and inhibiting the expression of Nrf2 promoted the proliferation of PRRSV. Further analysis showed that Nrf2 positively regulated the production of type I interferons and interferon-stimulated genes, which may contribute to its anti-PRRSV effect. By screening the PRRSV-encoded protein, we found that the PRRSV nsp5 protein can degrade Nrf2 at the protein level. Mechanistically, nsp5 promotes Nrf2-Keap1 binding affinity by inhibiting p62-mediated Keap1 sequestration and increasing Keap1 expression. Subsequently, this increased Keap1-mediated degradation of Nrf2 ubiquitination through K48-linked polyubiquitin. Furthermore, we found that the residues Tyr146 and Arg147 of nsp5 are crucial for inhibiting the activation of the p62-mediated Nrf2 antioxidant pathway. Thus, our findings uncover a novel mechanism by which PRRSV disrupts the host antioxidant defense system and highlight the crucial role of the Nrf2/HO-1 antioxidant pathway in host defense against PRRSV.IMPORTANCEOxidative stress-induced redox imbalance is a crucial pathogenic mechanism in viral infections. Nrf2 and its antioxidant genes serve as the main defense pathways against oxidative stress. However, the role of Nrf2 in the context of porcine reproductive and respiratory syndrome virus (PRRSV) infection remains unclear. In this study, we demonstrated that PRRSV infection decreased the expression of antioxidant genes of the Nrf2 signaling pathway and overexpression of Nrf2 triggered a strong anti-PRRSV effect. PRRSV nsp5 enhanced Keap1-dependent degradation of Nrf2 ubiquitination, thereby weakening cellular resistance to oxidative stress and antagonizing the antiviral activity of Nrf2. Our study further revealed a new mechanism by which PRRSV evades host antiviral innate immunity by disturbing cellular redox homeostasis, providing a new target for developing anti-PRRSV drugs.

Citrus tristeza virus p20 suppresses antiviral RNA silencing by co-opting autophagy-related protein 8 to mediate the autophagic degradation of SGS3.

Viruses exploit autophagy to degrade host immune components for their successful infection. However, how viral factors sequester the autophagic substrates into autophagosomes remains largely unknown. In this study, we showed that p20 protein, a viral suppressor of RNA silencing (VSR) encoded by citrus tristeza virus (CTV), mediated autophagic degradation of SUPPRESSOR OF GENE SILENCING 3 (SGS3), a plant-specific RNA-binding protein that is pivotal in antiviral RNA silencing. CTV infection activated autophagy, and the overexpression of p20 was sufficient to induce autophagy. Silencing of autophagy-related genes NbATG5 and NbATG7 attenuated CTV infection in Nicotiana benthamiana plants. In contrast, knockdown of the autophagy negative-regulated genes NbGAPCs led to virus accumulation, indicating the proviral role of autophagy in CTV infection. Further investigation found that p20 interacted with autophagy-related protein ATG8 through two ATG8-interacting motifs (AIMs) and sequestered SGS3 into autophagosomes by forming the ATG8-p20-SGS3 ternary complex. The mutations of the two AIMs in p20 (p20mAIM1 and p20mAIM5) abolished the interaction of p20 with ATG8, resulting in the deficiency of autophagy induction, SGS3 degradation, and VSR activity. Consistently, N. benthamiana plants infected with mutated CTVmAIM1 and CTVmAIM5 showed milder symptoms and decreased viral accumulation. Taken together, this study uncovers the molecular mechanism underlying how a VSR mediates the interplay between RNA silencing and autophagy to enhance the infection of a closterovirus.

CRISPR/Cas9-mediated editing of eukaryotic elongation factor 1B gamma (eEF1Bγ) reduces Tobacco etch virus accumulation in Nicotiana benthamiana

Key messageTobacco etch virus accumulation declined in Nicotiana benthamiana eEF1Bγ gene-edited lines, suggesting that eEF1Bγ may be a host factor for this virus.Viruses use host factors to replicate and move from cell to cell. Therefore, the editing of genes encoding viral host factors that are not essential for plant survival enables the rapid development of plants with durable virus resistance. Eukaryotic initiation factors, such as eIF4E and eIF4G, function as host factors for viral infection, and loss-of-function mutations of these factors lead to virus resistance. Broadening the spectrum of host factor targets would help expand resources for engineering virus resistance. In this study, we tested whether editing the eukaryotic translation elongation factor gene eEF1Bγ would produce virus-resistant plants. Accordingly, we targeted the four eEF1Bγ genes in Nicotiana benthamiana for editing using virus-induced gene editing (VIGE) with Tobacco rattle virus (TRV). Although we attempted to obtain plants edited for all four eEF1Bγ homologs, we failed to identify such plants. Instead, we obtained plants with three of the four homologs knocked out, harboring 1-bp insertion/deletions resulting in premature stop codons. These eEF1Bγ-edited plants did not exhibit resistance to Potato virus X (PVX), Tobacco mosaic virus (TMV), or Tomato bushy stunt virus (TBSV) but showed reduced accumulation of Tobacco etch virus (TEV) compared to wild-type plants. These findings demonstrate the feasibility of conferring resistance in plants through gene editing of eEF1Bγ, underscoring the importance of exploring diverse host factor targets for comprehensive virus resistance.

Deciphering Viral Replication Dynamics in Feline Infectious Peritonitis: A Quantitative Approach.

Feline infectious peritonitis (FIP) is a complex immune-mediated disease caused by feline coronavirus (FCoV). Despite advancements in understanding its pathogenesis, challenges persist in elucidating viral factors related to virion composition and replication. This study examined FCoV-infected cats with and without FIP for potential associations with or variation in expression ratios for different viral genes. We analyzed tissue samples with FIP lesions from 46 cats with FIP and mesenteric lymph nodes from 10 FCoV-infected cats (7b RT-qPCR positive) without FIP with three RT-qPCR assays, targeting (sub)-genomic RNAs of the RNA-dependent RNA polymerase (RdRp) and envelope (E) genes. In cats with FIP, the RdRp mRNA assay yielded the highest copy numbers, followed by the combined RdRp gRNA and mRNA assay; the E mRNA assay yielded the lowest copy numbers. In cats without FIP, significantly fewer viral RNA copies were detected regardless of the assay. Viral gene expression was not detected in six and was observed only at low levels in one or more assays in four samples. The observed correlation between assays and the intragroup correlation assay indicate consistent transcription of both the structural E protein and RdRp genes within FIP lesions in cats with FIP but not in cats with systemic FCoV infection alone.

HSV-1 ICP22 condensates impair host transcription by depleting promoter RNAPII Ser-2P occupation.

Herpes simplex virus type I (HSV-1) infection-induced host transcript ion shutdown is one of the most critical hallmarks of viral lytic infection. However, how HSV-1 and which viral factors accomplish this dramatic effect is not well understood. In this study, we show that ICP22-defined condensates shutdown host global transcription but facilitate viral transcription. This is independent of its effects on viral infection-triggered changes in splicing, readthrough, and read-in events. ICP22 condensates depleted the serine-2 phosphorylated RNA polymerase II (RNAPII Ser-2P) occupancy from the host transcription start site (TSS), resulting in decreased host transcripts output. At the same time, it ensures proper RNAPII Ser-2P distribution on the viral genome to promote viral transcription. This effect is dependent solely on the condensate-forming activity, as condensate-disrupting point mutations abolish it. In addition, ectopic expressed ICP22 alone could decrease host transcription activity and increase histone H3K27me3 modification level. Thus, ICP22 condensates shut down host transcription by reducing RNAPII binding to host TSS to impair the host transcription.

Neuropathogenesis of Old World Alphaviruses: Considerations for the Development of Medical Countermeasures.

Chikungunya virus (CHIKV) and other alphaviruses that primarily induce arthritogenic disease in humans, known as "Old World" alphaviruses, present an emerging public health concern as geographic ranges of mosquito vectors expand due to climate change. While a vaccine against CHIKV has recently been approved by several countries in North America and Europe, access to effective preventative countermeasures against disease induced by Old World alphaviruses remains elusive for the most vulnerable populations. Furthermore, treatment options continue to be limited to supportive care. Atypical neurological disease manifestations caused by Old World alphaviruses, which make up as many as 25% of the cases in some CHIKV outbreaks, present special challenges when considering strategies for developing effective countermeasures. This review focuses on Old World alphaviruses, specifically CHIKV, Ross River virus, O'nyoug-nyoug virus, and Mayaro virus, concentrating on the atypical neurological disease manifestations they may cause. Our current understanding of Old World alphavirus neuropathogenesis, gained from human cases and preclinical animal models, is discussed, including viral and host factors' roles in disease development. The current state of alphavirus preventatives and treatments, both virus-targeting and host-directed therapies, is then summarized and discussed in the context of addressing neurological disease induced by Old World alphaviruses.

Mucus Physically Restricts Influenza A Viral Particle Access to the Epithelium.

Prior work suggests influenza A virus (IAV) crosses the airway mucus barrier in a sialic acid-dependent manner through the actions of the viral envelope proteins, hemagglutinin, and neuraminidase. However, host and viral factors that influence how efficiently mucus traps IAV remain poorly defined. In this work, how the physicochemical properties of mucus influence its ability to effectively capture IAV is assessed using fluorescence video microscopy and multiple particle tracking. Our studies suggest an airway mucus gel layer must be produced with virus-sized pores to physically constrain IAV. While sialic acid binding by IAV may improve mucus trapping efficiency, sialic acid binding preference is found to have little impact on IAV mobility and the fraction of viral particles expected to penetrate the mucus barrier. Further, synthetic polymeric hydrogels engineered with mucus-like architecture are similarly protective against IAV infection despite their lack of sialic acid decoy receptors. Together, this work provides new insights on mucus barrier function toward IAV with important implications on innate host defense and transmission of respiratory viruses.

APOBEC3-Related Editing and Non-Editing Determinants of HIV-1 and HTLV-1 Restriction.

The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3/A3) family of cytosine deaminases serves as a key innate immune barrier against invading retroviruses and endogenous retroelements. The A3 family's restriction activity against these parasites primarily arises from their ability to catalyze cytosine-to-uracil conversions, resulting in genome editing and the accumulation of lethal mutations in viral genomes. Additionally, non-editing mechanisms, including deaminase-independent pathways, such as blocking viral reverse transcription, have been proposed as antiviral strategies employed by A3 family proteins. Although viral factors can influence infection progression, the determinants that govern A3-mediated restriction are critical in shaping retroviral infection outcomes. This review examines the interactions between retroviruses, specifically human immunodeficiency virus type 1 and human T-cell leukemia virus type 1, and A3 proteins to better understand how editing and non-editing activities contribute to the trajectory of these retroviral infections.

Mapping the viral battlefield: SARS-CoV-2 infection dynamics among healthcare workers in Brazil

BackgroundUnderstanding the dynamics of SARS-CoV-2 viral infection and factors associated with in-hospital transmission rates among healthcare workers (HCW) is crucial for their protection. Brazil experienced high mortality rates due to COVID-19, and limited data are available on transmission of SARS-CoV-2 infection among HCW. This cohort study aimed to assess the dynamic of SARS-CoV-2 infections in HCW from two tertiary hospitals in central Brazil, one of them a Reference Hospital for COVID-19.MethodsFrom May 2020 to January 2021, 554 HCW directly involved with COVID-19 care were followed through 12 biweekly visits. During these visits, blood, nasal, and oropharyngeal samples were collected, and participants underwent interviews. SARS-CoV-2 detection was carried out using RT-qPCR, while the assessment of seroprevalence was based on IgG detection. Additionally, 35 positive samples underwent viral whole-genome sequencing.ResultsThe infection prevalence, as per RT-qPCR, was 28.5% (24.9–32.4), reflecting an overall attack rate ranging from 0.5% to 9.5%, marked by two peaks in August and December 2020. Oligosymptomatic and asymptomatic infections accounted for 14% of prevalent infections. The seroprevalence rate stood at 25.8%. The hospitalization rate was 8.2%, with a fatality rate of 1.3%. Risk factors associated with a positive diagnosis of COVID-19 included being male, working at the referral hospital, having a graduate-education level, and using hydroxychloroquine and zinc for prevention or treatment. One reinfection was identified. Absenteeism was 56.6%. The infection dynamics mirrored the pattern observed in the general population.ConclusionOne-third of the professionals in the followed cohort were infected. Being male, working in a COVID-19 referral center, having a low level of education, and using medications for preventive treatment represented risk factors. Healthcare workers at the COVID-19 referral hospital exhibited a higher incidence rate compared to those at the non-referral hospital, increasing the plausibility that some of the infections occur in the hospital environment.

The Clinical Burden of SARS-CoV-2 Compared to Influenza A in the Same Cohort of Paediatric Outpatients; Increased Influenza Severity and Potential Insights.

The variation in the clinical severity of viral infections remains a matter of scientific debate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Influenza A virus (IAV) are both RNA viruses, exhibiting a range of clinical presentations, ranging from asymptomatic cases to fatalities, influenced by both viral and host factors. A descriptive real-life study was conducted, aiming to compare the clinical manifestations of recent COVID-19 with those of IAV infection in the same group of non-hospitalised, unvaccinated children. Between September 2021 and February 2023, we evaluated 115 individuals (male 48.7%, mean age 101.8 ± 50.8 months) who had not received vaccination for both SARS-CoV-2 and the quadrivalent influenza vaccine and were documented to be infected with both viruses within a 12-month time interval. The visual analogue scale (VAS-5) was used to assess parents'/patients' evaluation comparing the two infections. In cases of IAV infection, a significantly higher prevalence of prolonged high fever, upper and lower respiratory symptoms, and secondary infections was observed. The majority (74.8%) of patients and/or parents assessed IAV as a more severe clinical syndrome compared with SARS-CoV-2. The clinical burden of IAV was found to be greater than that of SARS-CoV-2 infection in the same unvaccinated children. This variation in clinical severity may provide a reference for effective vaccination policies; however, underlying mechanisms that could explain this difference require further evaluation.

A conserved lysine/arginine-rich motif is essential for the autophagic degradation of potyviral 6K1 protein and virus infection.

Potyviruses possess one positive-sense single-stranded RNA genome, mainly dependent on polyprotein processing as the expression strategy. The resulting polyproteins are proteolytically processed by three virus-encoded proteases into 11 or 12 mature proteins. One such factor, 6 kDa peptide 1 (6K1), is an understudied viral factor. Its function in viral infection remains largely mysterious. This study is to reveal part of its roles by using pepper veinal mottle virus (PVMV) as the model. Alanine substitution screening analysis revealed that 15 of 17 conserved residues across potyviral 6K1 sequences are essential for PVMV infection. However, 6K1 protein is less accumulated in virus-infected cells, although P3-6K1 and 6K1-CI junctions are efficiently processed by NIa-Pro for its release, indicating that 6K1 undergoes a self-degradation event. Mutating the cleavage site to prevent NIa-Pro processing abolishes viral infection, suggesting that the generation of 6K1 along with its degradation might be important for viral multiplication. We corroborated that cellular autophagy is engaged in 6K1's degradation. Individual engineering of the 15 6K1 variants into PVMV allows their expression along with viral infection. Five of such variants, D30A, V32A, K34A, L36A, and L39A, significantly interfere with viral infection. The five residues are enclosed in a conserved lysine/arginine-rich motif; four of them appear crucial in engaging autophagy-mediated self-degradation. Based on these data, we envisaged a scenario which potyviral 6K1s interact with an unknown anti-viral component to be co-degraded by autophagy to promote viral infection.IMPORTANCEPotyvirus is the largest genus of plant-infecting RNA viruses, which encompasses socio-economically important virus species, such as Potato virus Y, Plum pox virus, and Soybean mosaic virus. Like all picorna-like viruses, potyviruses express their factors mainly via polyprotein processing. Theoretically, viral factors P3 through CP, including 6K1, should share an equivalent number of molecules. The 6K1 is small in size (~6 kDa) and conserved across potyviruses but less accumulated in virus-infected cells. This study demonstrates that cellular autophagy is engaged in the degradation of 6K1 to promote viral infection. In particular, we found a conserved lysine/arginine-rich motif in 6K1s across potyviruses that is engaged in this degradation event. This finding reveals one facet of a small protein that helps understand the pro-viral role of cellular autophagy in viral infection.

Clinical and molecular analysis of JCPyV and BKPyV infection and associated risk of urothelial carcinoma development in the upper tract

BackgroundHuman polyomaviruses (HPyVs), JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV), have been found in upper tract urothelial carcinoma UTUC; however, the association of the viral oncogenic factors and clinical characteristics of UTUC remains unclear. This study aimed to investigate the prevalence of JCPyV and BKPyV in UTUC and their correlation with cancer progression among the southwest Taiwanese population from 2020 to 2022.MethodsA total of 72 paraffin-embedded UTUC tissue samples and 41 adjacent tissue samples were collected from 72 patients. Nested polymerase chain reaction and DNA sequencing were used to detect viral DNA and genotypes. Immunohistochemistry was performed using anti- large T (LT) and anti-p53 monoclonal antibodies to detect the expression of viral early LT protein and cellular p53 protein, respectively.ResultsThe overall prevalence of JCPyV and BKPyV were higher in UTUC than in adjacent tissue samples (65.3% [47/72] vs. 17.1% [7/41]). JCPyV and BKPyV were detected in 95.7% (45/47) and 4.3% (2/47) of the HPyVs-positive UTUC samples, respectively. JCPyV-TW-3 was the predominant strain of JCPyV infection. In UTUC samples, the LT protein of JCPyV and BKPyV positivity rate was 65.3%, while that of mutant p53 protein was 52.7%. JCPyV infection and LT protein expression increased the odds ratio (OR) of UTUC by 9.13-fold. The OR of UTUC was higher by 10.34-fold in patients with mutant p53 and by 10.37-fold in those with simultaneous LT and mutant p53 expression. The presence of LT protein in UTUC patients may increase the OR of mutant p53 protein expression by 2.93-fold compared to its absence. Women had a 5.19-fold higher superiority of JCPyV infection and LT expression than men. Patients with chronic kidney disease (CKD) had a 3.15-fold higher OR for mutant p53 protein expression than those without it. In the UTUC advanced stages, the OR of virus and LT expression was 3.18-fold higher compared to those who do not require chemotherapy.ConclusionsJCPyV infection is highly prevalent in UTUC, and the presence of CKD concurrent with high expressions of LT and mutant p53 proteins in patients may be a useful indicator for chemotherapy and poor prognosis.

Association between cadherin-related family member 3 rs6967330-A and human rhinovirus-C induced wheezing in children

BackgroundThe heterogeneity of childhood wheezing illnesses is associated with viral and host factors. Human rhinoviruses (HRV) are the major pathogens in severe wheezing in young children. The single nucleotide polymorphism (SNP) rs6967330 G > A proved to heighten the risk of wheezing. However, the relation between rs6967330 variants of cadherin-related family member 3 (CDHR3) and wheezing induced by human rhinovirus (HRV)-C has not been determined.MethodsA total of 11,756 respiratory specimens collected from hospitalized children with acute respiratory infections (ARIs) between September 2017 and March 2023 were screened for enterovirus (EV)/HRVs by the capillary electrophoresis-based multiplex PCR (CEMP) assay, and those positive only for HRVs were amplified and sequenced for HRV and CDHR3 genotyping. The clinical data of the enrolled patients were obtained and analyzed.ResultsEV/HRVs (15.2%; 1,616/10,608) were the more common viruses detected in inpatients with ARIs. Among the enrolled samples, 148 were positive for HRV-A (49.83%; 148/297), 129 for HRV-C (43.4%; 129/297), and 20 for HRV-B (6.7%; 20/297). More patients infected with HRV-C had history of allergy (P = 0.004), family history of asthma (P = 0.001), wheezing (P = 0.005) and asthma (P = 0.001) than those infected with HRV-A or HRV-B, while patients infected with HRV-C were less likely to have older siblings compared to those infected with HRV-A (P = 0.014). The rs6967330-A variant was related to a high incidence of the three concave signs (P = 0.047), asthma exacerbation (P = 0.025), a higher risk of HRV-C infection determined by the dominant model (OR 1.91, 95% confidence interval 1.05–3.48; P = 0.033), and a high proportion of wheezing (56.67%) in patients infected with HRV-C.ConclusionsHRV-C is the dominant species responsible for HRV-induced wheezing. The rs6967330-A variant is a risk factor for HRV-C infection, and was associated with the high rate of wheezing induced by HRV-C.

Dengue: epidemiology, diagnosis methods, treatment options, and prevention strategies.

Dengue is an arboviral disease caused by dengue virus, which is mostly found in tropical regions, and the number of human cases has increased dramatically since 2000, with 5.2million cases reported in 2019, according to WHO reports, 70% of which were in Southeast Asia, the Western Pacific, and Asia. Dengue infection can result in a wide range of clinical manifestations, ranging from fever to severe dengue shock syndrome, which can be fatal, particularly in those with secondary dengue. This review of the aetiology of dengue fever examines the complex interactions between the virus and the immune system and the interaction between viral and host factors and also covers outbreaks, the severity of disease caused by different serotypes, and methods for diagnosis of dengue, such as serological tests, nucleic acid amplification tests, and ELISA assays for detecting the NS1 antigen. Current treatment options and prevention strategies, including vector control measures, environmental interventions, and insect repellents are also discussed. This review highlights the challenges involved in developing a dengue vaccine, which is complicated by the need for an efficient and balanced immune response against all genotypes of the four serotypes.