Viruses-Basel最新文献

Dengue virus infection can cause severe complications due to vascular leakage. Angiopoietin-like protein 4 (ANGPTL4) regulates vascular permeability, but its role in dengue pathogenesis is unclear. This study investigated the association between plasma ANGPTL4 levels and dengue severity in Singapore adults. Plasma samples from 48 dengue patients (24 severe and 24 non-severe) during acute and convalescent phases were selected from the prospective COhort study on progression of DENgue severity in Singapore adults (CODEN) cohort. The CODEN was conducted at the National Centre for Infectious Diseases, Tan Tock Seng Hospital, from June 2016 to January 2020. ANGPTL4 levels were measured and compared to 152 healthy controls. Logistic regression assessed the relationship between plasma ANGPTL4 concentrations and disease severity. There were no statistically significant differences in ANGPTL4 levels between severe and non-severe dengue patients during acute (677.4 vs. 909.1 pg/mL, p = 0.4) or convalescent phases (793.7 vs. 565.6 pg/mL, p = 0.96). Plasma ANGPTL4 levels were significantly elevated during acute dengue (4634.3 pg/mL) versus healthy controls (907.4 pg/mL), declining during convalescence. Compared to the lowest tertile, the adjusted odds ratios for severe dengue were 0.36 (95%CI: 0.08-1.65, p = 0.190) for medium tertile and 0.57 (95%CI: 0.13-2.49, p = 0.456) for high tertile. Among patients with high ANGPTL4 levels (>5000 pg/mL), 36.4% developed severe complications, including significant plasma leakage. Plasma ANGPTL4 levels were significantly higher in dengue patients than controls, suggesting its potential as a biomarker, which warrants future detailed investigations. Larger prospective studies with serial sampling, including pediatric populations, may clarify the role of ANGPTL4 in severe dengue.

Feline coronavirus (FCoV) is an alphacoronavirus (αCoV) that causes moderate or chronic asymptomatic infection in cats. However, in a single infected cat, FCoV can modify its cellular tropism by acquiring the ability to infect macrophages, resulting in the development of feline infectious peritonitis (FIP). In this context, to restrain the impact of FCoV infection, scientific research has focused attention on the development of antiviral therapies involving novel mechanisms of action. Recent studies have demonstrated that aryl hydrocarbon receptor (AhR) signaling regulates the host response to different human and animal CoVs. Hence, the mechanism of action of AhR was evaluated upon FCoV infection in Crandell Feline Kidney (CRFK) and in canine fibrosarcoma (A72) cells. Following infection with feline enteric CoV (FECV), strain "München", a significant activation of AhR and of its target CYP1A1, was observed. The selective AhR antagonist CH223191 provoked a reduction in FCoV replication and in the levels of viral nucleocapsid protein (NP). Furthermore, the effect of the AhR inhibitor on the acidity of lysosomes in infected cells was observed. Our findings indicate that FCoV acts on viral replication that upregulates AhR. CH223191 repressed virus yield through the inhibition of AhR. In this respect, for counteracting FCoV, AhR represents a new target useful for identifying antiviral drugs. Moreover, in the presence of CH223191, the alkalinization of lysosomes in FCoV-infected CRFK cells was detected, outlining their involvement in antiviral activity.

Diagnostic testing plays a key role in a surveillance program as diagnostic testing aims to accurately determine the infection or disease status of an individual animal. Diagnostic assays for AIV can be categorized into four broad types: tests for detecting the virus, its antigen, its genomic material, and antibodies to the virus. Virus characterization almost always follows virus detection. The present article surveys the current literature on the goals, principles, test performance, advantages, and disadvantages of these diagnostic assays. Virus isolation can be achieved using embryonating eggs or cell cultures in a lab setting. Virus antigens can be detected by antigen-capturing immunoassays or tissue immunoassays. Viral RNA can be detected by PCR-based assays (gel-based reverse transcription-polymerase chain reaction (RT-PCR), or probe or SYBR^® Green-based real-time RT-PCR), loop-mediated isothermal amplification, in situ hybridization, and nucleic acid sequence-based amplification. Antibodies to AIV can be detected by ELISA, agar gel immunodiffusion, hemagglutination inhibition, and microneutralization. Avian influenza virus can be characterized by hemagglutination inhibition, neuraminidase inhibition, sequencing (dideoxynucleotide chain-termination sequencing, next-generation sequencing), genetic sequence-based pathotype prediction, and pathogenicity testing. Novel and variant AIVs can be recognized by DNA microarrays, electron microscopy, mass spectroscopy, and Biological Microelectromechanical Systems. A variety of diagnostic tests are employed in AIV surveillance and monitoring. The choice of their use depends on the goal of testing (fit for purpose), the time of testing during the disease, the assay target, the sample matrix, assay performance, and the advantages and disadvantages of the assay. The article concludes with authors' perspective of the use of diagnostic assays in the surveillance and monitoring of AIV in poultry.

Arthropod-borne viruses (arboviruses) dengue (DENV), chikungunya (CHIK), and Zika (ZIKV) have been responsible for a high number of outbreaks worldwide. However, their screening in blood donors is not mandatory, and asymptomatic cases might act as an important cause of virus transmission via transfusion. A study was conducted to assess the presence of DENV (serotypes 1-4), ZIKV, and CHIKV in pooled samples (pool size: six) from asymptomatic blood donors. A total of 9463 plasma pools, corresponding to 56,778 blood donations from asymptomatic blood donors who attended donor sessions at HEMORIO and other blood centers in Rio de Janeiro and Espírito Santo, was submitted to automated nucleic-acid extraction and PCR amplification using ZC D-Tipagem molecular assay (Bio-Manguinhos). In general, a pool prevalence of 1% (95/9463) and a donor prevalence of 0.17% (95/56,778) were observed. January and February 2024 had a total of 62 positive pools out of 95 (65.3%). Targets DENV-1 and -2 had a higher prevalence in the studied months-early summer-with 24 and 28 positive pools, respectively. ZC D-Tipagem molecular assay was able to detect the best-known arboviruses circulating in asymptomatic blood donors; this study suggested that ZIKV, CHIK, and DENV are circulating in asymptomatic blood donors before blood donations and can be transmitted to blood transfusion recipients.

Noroviruses represent one of the leading causes of outbreaks and sporadic acute gastroenteritis (AGE) cases across all age groups. Although the GII.4 norovirus has been identified as the primary cause of most AGE outbreaks, the transient predominance of other genotypes has been reported globally. In this study, we describe a multi-province AGE outbreak caused by a potential new lineage of norovirus GII.17[P17], which has been recently detected at a high incidence in the United States and Europe. An amino acid analysis of the major viral capsid protein revealed several substitutions in the hypervariable region compared to strains circulating in the mid-2010s, which could play a key role in immune evasion. This is the first report of the detection of these viruses in the Southern Hemisphere, underscoring the importance of maintaining active genomic surveillance in the context of increasing numbers of acute gastroenteritis outbreaks.

To identify measures that mitigate the impact of influenza in Latin America and the Caribbean, we compared the burden and detection capacity in humans and animals after the 2009 pandemic. The incidence rate in people was higher in Chile (23.72 per 100,000 people), but the impact was greater for Guatemala (503.78 disability-adjusted life years per 100,000 people). Brazil, Peru, Argentina, and Mexico built better medical testing, with typing being less frequent in Chile and Argentina, where costs for medical care were higher. The positivity rate among avian and nonhuman mammals was 5.8%, with more cases in Mexico, but constant testing in Chile. H5N1, H5N2, and H7N6 are deadly to poultry, whereas H1N1 is common in swine, and H3N8 in equines. By June 2023, H5N1 had caused severe influenza in two persons and killed millions of birds and hundreds of mammals with aquatic lifestyles. An analysis of the efforts in response to this outbreak revealed that handling of outbreaks in animals needs homogeneity and reinforcement of vaccination. Surveillance in exposed individuals requires articulation of medical and animal health authorities, and the region also demands decentralized typing and networks for genomic characterization.

I started my research career (in 1965) on interferon by identifying polyacrylic acid (PAA) as an interferon inducer. Poly(I).poly(C), discovered by Maurice Hilleman's group, proved to be more potent as an interferon inducer, and through its mRNA, we were able to clone and express human β-interferon. The discovery of the reverse transcriptase (RT) by Temin and Baltimore (in 1970) brought me to the detection of suramin as a powerful RT inhibitor and enabled Sam Broder and his colleagues to identify suramin as the first inhibitor of HIV replication. In this capacity, it was subsequently superseded by AZT and other 2',3'-dideoxynucleoside (ddN) analogs, including d4T. In collaboration with Antonín Holý, we discovered several acyclic nucleoside phosphonates as potent inhibitors of both HIV and HBV (hepatitis B virus) replication. In collaboration with Paul Janssen, we identified various non-nucleoside RT inhibitors (NNRTIs) of HIV-1 replication. Of the nucleotide RT inhibitors (NtRTTs), tenofovir emerged as the most promising congener. It was derivatized to its oral prodrugs TDF and TAF. To enhance their efficacy, they were combined with other anti-HIV drugs, and two of them were pursued (and found efficacious) in the Pre-Exposure Prophylaxis (PrEP) of HIV infections.

Background: In 2024, mainland China witnessed a significant upsurge in Hand, Foot, and Mouth Disease (HFMD) cases. Coxsackievirus A16 (CVA16) is one of the primary causative agents of HFMD. Long-term monitoring of theCVA16 infection rate and genotype changes is crucial for the prevention and control of HFMD.

Methods: A total of 40,673 clinical specimens were collected from suspected HFMD cases in Guangdong province from 2018 to 2024, including rectal swabs (n = 27,954), throat swabs (n = 6791), stool (n = 5923), cerebrospinal fluid (n = 3), and herpes fluid (n = 2). A total of 24,410 samples were detected as EV-positive and further typed by RT-PCR. A total of 872 CVA16-positive samples were isolated and further sequenced to obtain the full-length VP1 sequence. Phylogenetic analysis was performed based on viral protein 1 gene (VP1).

Results: In the first 25 weeks of 2024, reported cases of HFMD were 1.36 times higher than the mean rates of 2023. In 2024, CVA16 predominated at 75.42%, contrasting with the past etiological pattern in which the CVA6 was predominant with the detection rate ranging from 32.85 to 77.61% from 2019 to 2023. Phylogenetic analysis based on the VP1 gene revealed that the B1a and B1b subtypes co-circulated in Guangdong from 2018 to 2022. The B1c outbreak clade, detected in Guangdong in 2023, constituted 68.24% of the 148 strains of CVA16 collected in 2024, suggesting a subtype shift in the CVA16 virus. There were three specific amino acid variations (P3S, I235V, and T240A) in the VP1 sequence of B1c.

Conclusions: The new emergence of the CVA16 B1c outbreak clade in Guangdong during 2023-2024 highlights the necessity for the enhanced surveillance of the virus evolution epidemiological dynamic in this region. Furthermore, it is imperative to closely monitor the etiological pattern changes in Hand, Foot, and Mouth Disease (HFMD) in other regions as well. Such vigilance will be instrumental in guiding future vaccination strategies for HFMD.

The number of new cancer cases is soaring, and currently, there are 440.5 per 100,000 new cases reported every year. A quarter of these are related to human papillomavirus (HPV) infections, particularly types 16 and 18. These include oropharyngeal, anal, vaginal, and penile cancers. A critical aspect of their oncogenic potential lies in their ability to manipulate host immune responses, facilitating immune evasion and carcinogenesis. High-risk HPVs target key immune components like granzymes A and B and MHC-I, which are crucial for the elimination of virus-infected and transformed cells, thereby weakening immune surveillance. Evidence suggests that high-risk HPVs downregulate the expression of tumor suppressors, such as p53 and pRB, and the activity of these immune components, weakening CTL and NK cell responses, thus enabling persistent infection and carcinogenesis. We discuss the implications of granzyme and MHC-I dysregulation for immune evasion, tumor progression, and potential therapeutic strategies. This review further explores the regulation of granzyme A, B, and MHC-I by high-risk HPVs, focusing on how viral oncoproteins, E6 and E7, interfere with granzyme-mediated cytotoxicity and antigen presentation. The complex interplay between high-risk HPVs, granzyme A, granzyme B, and MHC-I may provide insights into novel approaches for targeting HPV-associated cancers.

Human parvovirus B19 (B19V) is a major human pathogen in which the ssDNA genome is replicated within the nucleus of infected human erythroid progenitor cells (EPCs) through a process involving both cellular and viral proteins, including the non-structural protein (NS)1. We previously characterized the interaction between NS1 classical nuclear localization signal (cNLS: GACHAKKPRIT-182) and host cell importin (IMP)α and proposed it as a potential target for antiviral drug development. Here, we further extend on such findings. First, we demonstrate that NS1 nuclear localization is required for viral production since introducing the K177T substitution in a cloned, infectious viral genome resulted in a non-viable virus. Secondly, we demonstrate that the antiparasitic drug ivermectin (IVM), known to inhibit the IMPα/β dependent nuclear import pathway, could impair the NS1-NLS:IMPα interaction and suppress viral replication in UT7/EpoS1 cells in a dose-dependent manner. We also show that a panel of structurally related avermectins (AVMs) can dissociate the NS1-NLS:IMPα complex with half-maximal inhibitory concentrations in the nanomolar range. Among them, Eprinomectin emerged as the most selective inhibitor of B19V replication, with a selectivity index of c. 5.0. However, when tested in EPCs generated from peripheral blood mononuclear cells, which constitute a cellular population close to the natural target cells in bone marrow, the inhibitory effect of IVM and Eprinomectin was demonstrated to a lesser extent, and both compounds exhibited high toxicity, thus highlighting the need for more specific inhibitors of the NS1-NLS:IMPα interaction.