Virology最新文献

While phages hold promise as an antibiotic alternative, they encounter significant challenges in combating bacterial infections, primarily due to the emergence of phage-resistant bacteria. Bacterial defence mechanisms like superinfection exclusion, CRISPR, and restriction-modification systems can hinder phage effectiveness. Innovative strategies, such as combining different phages into cocktails, have been explored to address these challenges. This review delves into these defence mechanisms and their impact at each stage of the infection cycle, their challenges, and the strategies phages have developed to counteract them. Additionally, we examine the role of phage cocktails in the evolving landscape of antibacterial treatments and discuss recent studies that highlight the effectiveness of diverse phage cocktails in targeting essential bacterial receptors and combating resistant strains.

Barramundi aquaculture is at risk of severe disease outbreaks and massive production losses. Here we used bioinformatics to screen 84 farmed barramundi transcriptomes to identify novel viruses that could threaten barramundi aquaculture and to establish a barramundi aquaculture virome. We discovered five novel viruses: latid herpesvirus 1 (LatHV-1) from the Alloherpesviridae family, barramundi parvovirus 1 (BParV1) from the Parvoviridae family, barramundi calicivirus 1 (BCaV1) from the Caliciviridae family, and barramundi associated picorna-like virus 1 and 2 (BPicV1 and BPicV2) from the Picornaviridae family. LatHV-1, BCaV1, and BParV1 are closely related to pathogenic viruses found in other fish species that can cause mass mortality in farms. To aid in future viral surveillance, we also designed and successfully tested an RT-PCR assay for the detection of BCaV1. Overall, we discovered a range of pathogenic viruses in barramundi aquaculture, paving the way for developing effective detection methods to assist early outbreak management.

Hepatitis B virus is one of the leading causes behind the neoplastic transformation of liver tissue and associated mortality. Despite the availability of many therapies and vaccines, the pathogenic landscape of the virus remains elusive; urging the development of novel strategies based on the fundamental infectious and transformative modalities of the virus-host interactome. Ubiquitination is a widely observed post-translational modification of several proteins, which either regulates the proteins' turnover or impacts their functionalities. In recent years, ample amount of literature has accumulated regarding the ubiquitination dynamics of the HBV proteins as well as the host proteins during HBV infection and carcinogenesis; with direct and detailed characterization of the involvement of HBV in these processes. Interestingly, while many of these ubiquitination events restrict HBV life cycle and carcinogenesis, several others promote the emergence of hepatocarcinoma by putting the virus in an advantageous position. This review sums up the snowballing literature on ubiquitination-mediated regulation of the host-HBV crosstalk, with special emphasis on its influence on the establishment and progression of hepatocellular carcinoma on a molecular level. With the advent of cutting-edge ubiquitination-targeted therapeutic approaches, the findings emanating from this review may potentiate the identification of novel anti-HBV targets for the formulation of novel anticancer strategies to control the HBV-induced hepato-carcinogenic process on a global scale.

Positive-strand RNA viruses build viral replication organelles (VROs) with the help of co-opted host factors. The biogenesis of the membranous VROs requires major metabolic changes in infected cells. Previous studies showed that tomato bushy stunt virus (TBSV) hijacks several glycolytic enzymes to produce ATP locally within VROs. In this work, we demonstrate that the yeast Pfk2p phosphofructokinase, which performs a rate-limiting and highly regulated step in glycolysis, interacts with the TBSV p33 replication protein. Deletion of PFK2 reduced TBSV replication in yeast, suggesting proviral role for Pfk2p. TBSV also co-opted two plant phosphofructokinases, which supported viral replication and ATP production within VROs, thus acting as proviral factors. Three other phosphofructokinases inhibited TBSV replication and they reduced ATP production within VROs, thus functioning as antiviral factors. Altogether, different phosphofructokinases have proviral or antiviral roles. This suggests on-going arms race between tombusviruses and their hosts to control glycolysis pathway in infected cells.

Viral spike proteins mutate frequently, but conserved features within these proteins often have functional importance and can inform development of anti-viral therapies which circumvent the effects of viral sequence mutations. Through analysis of large numbers of viral spike protein sequences from several viral families, we found highly (>99%) conserved patterns within their intracellular domains. The patterns generally consist of one or more basic amino acids (arginine or lysine) adjacent to a cysteine, many of which are known to undergo acylation. These patterns were not enriched in cellular proteins in general. Molecular dynamics simulations show direct electrostatic and hydrophobic interactions between these conserved residues in hemagglutinin (HA) from influenza A and B and the phosphoinositide PIP2. Super-resolution microscopy shows nanoscale colocalization of PIP2 and several of the same viral proteins. We propose the hypothesis that these conserved viral spike protein features can interact with phosphoinositides such as PIP2.

This study assesses different IBV vaccination regimens in broiler chickens using commercially available live attenuated GI-23 (Egyptian-VAR2) and GI-1 (H120) vaccines. Vaccines were administered at 1, 14 days of age, or both. The ciliostasis test, following wild-type VAR2 challenge at 28 days of age, indicated that classic H120+VAR2 at one day old followed by the VAR2 vaccine at 14 days of age provided the highest level of protection (89.58%). Similarly, administering VAR2 at 1 day of age and classic H120 at 14 days of age demonstrated substantial protection (85.42%). Conversely, administering only classic H120 and VAR2 at one day old resulted in the lowest protection level (54.17%). Tracheal virus shedding quantification and assessment of trachea and kidney degenerative changes were significantly lower in vaccinated groups compared to the unvaccinated-challenged group. In conclusion, a carefully planned vaccination regimen based on homologous vaccination offers the most effective clinical protection in broiler chickens.

In vitro studies have shown that deletion of nef and deleterious mutation in the Nef dimerization interface attenuates HIV replication and associated pathogenesis. Humanized rodents with human immune cells and lymphoid tissues are robust in vivo models for investigating the interactions between HIV and the human immune system. Here, we demonstrate that nef deletion impairs HIV replication and HIV-induced immune dysregulation in the blood and human secondary lymphoid tissue (human spleen) in bone marrow-liver-thymus-spleen (BLTS) humanized mice. Furthermore, we also show that nef defects (via deleterious mutations in the dimerization interface) impair HIV replication and HIV-induced immune dysregulation in the blood and human spleen in BLTS-humanized mice. We demonstrate that the reduced replication of nef-deleted and nef-defective HIV is associated with robust antiviral innate immune response, and T helper 1 response. Our results support the proposition that Nef may be a therapeutic target for adjuvants in HIV cure strategies.

Merkel cell carcinoma (MCC) is an extremely rare cutaneous neuroendocrine cancer, with an incidence approximately 40 times lower than that of malignant melanoma; however, its significantly inferior survival rate compared to melanoma establishes MCC as the most lethal form of skin cancer. In recent years, a substantial body of literature has demonstrated a gradual increase in the incidence of MCC. Although the two factors that contribute to MCC, ultraviolet radiation and Merkel cell polyomavirus infection, have been well established, the specific pathogenesis of this disease remains unclear. Additionally, considering the high lethality and recurrence rates of MCC, as well as the absence of specific antitumor drugs, it is crucial to elucidate the factors that can accurately predict patients' outcomes. In this review, we summarized the significant advancements in the epidemiological characteristics, pathogenesis, and the factors that influence patient prognosis of MCC to enhance clinical practices and public health efforts.

RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.

Among group A rotaviruses (RVAs), the G1 genotype is the main genotype causing diarrhea in children, but it has rarely been reported in pigs. During our epidemiological investigation, we detected G1P[7] rotavirus infection in piglets across several provinces in China and then isolated a porcine G1P[7] rotavirus strain (CN1P7). Sequencing revealed that the virus constellation was G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. Phylogenetic analyses revealed that CN1P7 most likely emerged due to genetic reassortment among porcine, human, giant panda and dog rotavirus strains. In vivo experiments were conducted on two-day-old piglets, which revealed that the CN1P7 strain was pathogenic to piglets. The virus was shed through the digestive tract and respiratory tract. In addition to the intestine, the CN1P7 strain displayed extraintestinal tropisms in piglets. Histopathological analysis revealed that the lung and small intestine were the targets of CN1P7. This study is the first to explore the molecular and pathogenic characterization of a pig-origin G1P[7] rotavirus.