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Virology Sep 2023Varicella-zoster virus (VZV) is a highly infectious DNA virus that can cause varicella (chickenpox) and herpes zoster (HZ). A simple, sensitive and specific detection...
Varicella-zoster virus (VZV) is a highly infectious DNA virus that can cause varicella (chickenpox) and herpes zoster (HZ). A simple, sensitive and specific detection method is desirable for the VZV infection. In this study, VZV gE protein, expressed in CHO cells, was used to immunize BALB/c mice for the generation of monoclonal antibodies (mAbs). For the first time, we developed a colloidal gold-based immunochromatographic strip for rapid detection of VZV using a pair of mAbs against gE protein. The limit of detection (LOD) of the strip was 30 ng mL of purified VZV gE antigen, and it could specifically test VZV without cross-reactivity with Enterovirus 71 (EV-71), Herpes simplex virus 1 (HSV-1) and Herpes simplex virus 2 (HSV-2). The coincidence rate between the strip and commercial real-time PCR diagnostic kit was 100% using vesicle as the clinical sample. Our strip provided a technical support for rapid and specific detection of VZV.
Topics: Animals; Mice; Cricetinae; Herpesvirus 3, Human; Cricetulus; Antibodies, Viral; Herpes Zoster; Chickenpox; Herpesvirus 2, Human; Antibodies, Monoclonal
PubMed: 37481958
DOI: 10.1016/j.virol.2023.07.008 -
Microbial Pathogenesis Sep 2023Epigenetics, a field of study focused on cellular gene regulation independent of DNA sequence alterations, encompasses DNA methylation, histone modification and microRNA... (Review)
Review
Epigenetics, a field of study focused on cellular gene regulation independent of DNA sequence alterations, encompasses DNA methylation, histone modification and microRNA modification. Epigenetics processes play a pivotal role in governing the life cycles of viruses, enabling their transmission, persistence, and maintenance with in host organisms. This review examines the epigenetics regulation of diverse virus including orthomoxyviruses, coronavirus, retroviridae, mononegavirales, and poxviruses among others. The investigation encompasses ten representative viruses from these families. Detailed exploration of the epigenetic mechanisms underlying each virus type, involving miRNA modification, histone modification and DNA methylation, sheds light on the intricate and multifaceted epigenetic interplay between viruses and their hosts. Furthermore, this review investigates the influence of these epigenetic processes on infection cycles, emphasizing the utilization of epigenetics by viruses such as Epstein-Barr virus and Human immunodeficiency virus (HIV) to regulate gene expression during chronic or latent infections, control latency, and transition to lytic infection. Finally, the paper explores the novel treatments possibilities stemming from this epigenetic understanding.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Host Microbial Interactions; Epigenesis, Genetic; Viruses
PubMed: 37517745
DOI: 10.1016/j.micpath.2023.106271 -
Antiviral Therapy Aug 2023In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease... (Review)
Review
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
Topics: Humans; Hepatitis B virus; Antiviral Agents; Coinfection; Hepacivirus; Hepatitis C, Chronic; Ribavirin; Liver Cirrhosis; Interferons; Liver Neoplasms
PubMed: 37489502
DOI: 10.1177/13596535231189643 -
Science Bulletin Oct 2023Mountain and polar glaciers cover 10% of the Earth's surface and are typically extreme environments that challenge life of all forms. Viruses are abundant and active in...
Mountain and polar glaciers cover 10% of the Earth's surface and are typically extreme environments that challenge life of all forms. Viruses are abundant and active in supraglacial ecosystems and play a crucial role in controlling the supraglacial microbial communities. However, our understanding of virus ecology on glacier surfaces and their potential impacts on downstream ecosystems remains limited. Here, we present the supraglacial virus genome (SgVG) catalog, a 15-fold expanded genomic inventory of 10,840 DNA-virus species from 38 mountain and polar glaciers, spanning habitats such as snow, ice, meltwater, and cryoconite. Supraglacial DNA-viruses were highly specific compared to viruses in other ecosystems yet exhibited low public health risks. Supraglacial viral communities were primarily constrained by habitat, with cryoconite displaying the highest viral activity levels. We observed a prevalence of lytic viruses in all habitats, especially in cryoconite, but a high level of lysogenic viruses in snow and ice. Additionally, we found that supraglacial viruses could be linked to ∼83% of obtained prokaryotic phyla/classes and possessed the genetic potential to promote metabolism and increase cold adaptation, cell mobility, and phenolic carbon use of hosts in hostile environmental conditions using diverse auxiliary metabolic genes. Our results provide the first systematic characterization of the diversity, function, and public health risks evaluation of mountain and polar supraglacial DNA viruses. This understanding of glacial viruses is crucial for function assessments and ecological modeling of glacier ecosystems, especially for the Tibetan Plateau's Mountain glaciers, which support ∼20% of the human populations on Earth.
Topics: Humans; Ice; Microbiota; DNA Viruses; DNA
PubMed: 37739838
DOI: 10.1016/j.scib.2023.09.007 -
Viruses Nov 2023The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1,... (Review)
Review
The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.
Topics: Humans; Animals; Antiviral Agents; Flavonoids; Herpes Simplex; Herpesvirus 1, Human; Life Cycle Stages
PubMed: 38140581
DOI: 10.3390/v15122340 -
Viruses Jul 2023An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus... (Review)
Review
An enveloped double-stranded DNA monkeypox virus (MPXV) is a causative agent of the zoonotic viral disease, human monkeypox (HMPX). MPXV belongs to the genus Orthopoxviridae, a family of notorious smallpox viruses, and so it shares similar clinical pathophysiological features. The recent multicountry HMPX outbreak (May 2022 onwards) is recognized as an emerging global public health emergency by the World Health Organization, shunting its endemic status as opined over the past few decades. Re-emergence of HMPX raises concern to reassess the present clinical strategy and therapeutics as its outbreak evolves further. Keeping a check on these developments, here we provide insights into the HMPX epidemiology, pathophysiology, and clinical representation. Weighing on its early prevention, we reviewed the strategies that are being enrolled for HMPX diagnosis. In the line of expanded MPXV prevalence, we further reviewed its clinical management and the diverse employed preventive/therapeutic strategies, including vaccines (JYNNEOS, ACAM2000, VIGIV) and antiviral drugs/inhibitors (Tecovirimat, Cidofovir, Brincidofovir). Taken together, with a revised perspective of HMPX re-emergence, the present report summarizes new knowledge on its prevalence, pathology, and prevention strategies.
Topics: Humans; Animals; Mpox (monkeypox); Monkeypox virus; Disease Outbreaks; Zoonoses
PubMed: 37515218
DOI: 10.3390/v15071533 -
International Journal of Molecular... Nov 2023Herpesviruses are large DNA viruses that have long been used as powerful gene therapy tools. In recent years, the ability of herpesviruses to stimulate both innate and... (Review)
Review
Herpesviruses are large DNA viruses that have long been used as powerful gene therapy tools. In recent years, the ability of herpesviruses to stimulate both innate and adaptive immune responses has led to their transition to various applications as vaccine vectors. This vaccinology branch is growing at an unprecedented and accelerated rate. To date, human herpesvirus-based vectors have been used in vaccines to combat a variety of infectious agents, including the Ebola virus, foot and mouth disease virus, and human immunodeficiency viruses. Additionally, these vectors are being tested as potential vaccines for cancer-associated antigens. Thanks to advances in recombinant DNA technology, immunology, and genomics, numerous steps in vaccine development have been greatly improved. A better understanding of herpesvirus biology and the interactions between these viruses and the host cells will undoubtedly foster the use of herpesvirus-based vaccine vectors in clinical settings. To overcome the existing drawbacks of these vectors, ongoing research is needed to further advance our knowledge of herpesvirus biology and to develop safer and more effective vaccine vectors. Advanced molecular virology and cell biology techniques must be used to better understand the mechanisms by which herpesviruses manipulate host cells and how viral gene expression is regulated during infection. In this review, we cover the underlying molecular structure of herpesviruses and the strategies used to engineer their genomes to optimize capacity and efficacy as vaccine vectors. Also, we assess the available data on the successful application of herpesvirus-based vaccines for combating diseases such as viral infections and the potential drawbacks and alternative approaches to surmount them.
Topics: Humans; Herpesviridae; Simplexvirus; Virus Diseases; Viral Vaccines; Genetic Vectors
PubMed: 38003300
DOI: 10.3390/ijms242216112 -
Emerging Microbes & Infections Dec 2023In recent years, an increasing number of emerging and remerging virus outbreaks have occurred and the rapid development of vaccines against these viruses has been...
In recent years, an increasing number of emerging and remerging virus outbreaks have occurred and the rapid development of vaccines against these viruses has been crucial. Controlling the replication of premature termination codon (PTC)-containing viruses is a promising approach to generate live but replication-defective viruses that can be used for potent vaccines. Here, we used anticodon-engineered transfer RNAs (ACE-tRNAs) as powerful precision switches to control the replication of PTC-containing viruses. We showed that ACE-tRNAs display higher potency of reading through PTCs than genetic code expansion (GCE) technology. Interestingly, ACE-tRNA has a site preference that may influence its read-through efficacy. We further attempted to use ACE-tRNAs as a novel viral vaccine platform. Using a human immunodeficiency virus type 1 (HIV-1) pseudotyped virus as an RNA virus model, we found that ACE-tRNAs display high potency for read-through viral PTCs and precisely control their production. Pseudorabies virus (PRV), a herpesvirus, was used as a DNA virus model. We found that ACE-tRNAs display high potency for reading through viral PTCs and precisely controlling PTC-containing virus replication. In addition, PTC-engineered PRV completely attenuated and lost virulence in mice , and immunization with PRV containing a PTC elicited a robust immune response and provided complete protection against wild-type PRV challenge. Overall, replication-controllable PTC-containing viruses based on ACE-tRNAs provide a new strategy to rapidly attenuate virus infection and prime robust immune responses. This technology can be used as a platform for rapidly developing viral vaccines in the future.
Topics: Humans; Mice; Animals; Swine; Pseudorabies; Viral Vaccines; Herpesvirus 1, Suid; Vaccination; RNA, Transfer; Antibodies, Viral; Swine Diseases
PubMed: 36482724
DOI: 10.1080/22221751.2022.2157339 -
Nature Structural & Molecular Biology Mar 2024Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus...
Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2-48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus-host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.
Topics: Humans; Hepatitis B virus; Hepatocytes; Protein Binding; Virus Attachment; Peptides; Symporters; Virus Internalization
PubMed: 38233573
DOI: 10.1038/s41594-023-01191-5 -
ACS Chemical Biology Aug 2023The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and the world food supply. This...
The constant and the sudden emergence of zoonotic human and animal viruses is a significant threat to human health, the world economy, and the world food supply. This has necessitated the development of broad-spectrum therapeutic strategies to combat these emerging pathogens. Mechanisms that are essential for viral replication and propagation have been successfully targeted in the past to develop broad-spectrum therapeutics that can be readily repurposed to combat new zoonotic pathogens. Because of the importance of viral RNA capping enzymes to viral replication and pathogenesis, as well as their presence in both DNA and RNA viruses, these viral proteins have been a long-standing therapeutic target. Here, we use genome sequencing information and yeast-based platforms (YeRC0M) to identify, characterize, and target viral genome-encoded essential RNA capping enzymes from emerging strains of DNA viruses, i.e., Monkeypox virus and African Swine Fever Virus, which are a significant threat to human and domestic animal health. We first identified and biochemically characterized these viral RNA capping enzymes and their necessary protein domains. We observed significant differences in functional protein domains and organization for RNA capping enzymes from emerging DNA viruses in comparison to emerging RNA viruses. We also observed several differences in the biochemical properties of these viral RNA capping enzymes using our phenotypic yeast-based approaches (YeRC0M) as compared to the previous in vitro studies. Further, using directed evolution, we were able to identify inactivation and attenuation mutations in these essential viral RNA capping enzymes; these data could have implications on virus biocontainment as well as live attenuated vaccine development. We also developed methods that would facilitate high-throughput phenotypic screening to identify broad-spectrum inhibitors that selectively target viral RNA capping enzymes over host RNA capping enzymes. As demonstrated here, our approaches to identify, characterize, and target viral genome-encoded essential RNA capping enzymes are highly modular and can be readily adapted for targeting emerging viral pathogens as well as their variants that emerge in the future.
Topics: Animals; Humans; Swine; Saccharomyces cerevisiae; African Swine Fever Virus; Viruses; RNA, Viral; Virus Replication; DNA Viruses
PubMed: 37498174
DOI: 10.1021/acschembio.3c00243