-
Journal of the Formosan Medical... Sep 2014Virus-associated human cancers may exhibit two characteristic histopathologic features: (1) the inflammation-rich background as observed in Epstein-Barr virus-associated... (Review)
Review
Virus-associated human cancers may exhibit two characteristic histopathologic features: (1) the inflammation-rich background as observed in Epstein-Barr virus-associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC); and (2) the characteristic nuclear morphology such as the Reed-Sternberg cells in HL. Besides, the hepatocytes of chronic hepatitis B virus (HBV) infection frequently exhibit characteristic ground glass hepatocytes, a phenomenon associated with endoplasmic reticulum stress response induced by the overloaded or malfolded HBV surface antigens. In this review, we explore specifically the pathogenesis of Epstein-Barr virus-associated HL and NPC, and HBV-associated hepatocellular carcinoma based on the observed histopathologic features. We propose that the retention of viral proteins induces inflammation, endoplasmic reticulum stress, and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the viral oncoproteins may play additional transactivational roles to induce host genes for transformation, invasion, and metastasis. Therapeutic implications based on the pathogenesis of virus-associated cancers are discussed.
Topics: Animals; DNA, Viral; Hepatitis B virus; Herpesvirus 4, Human; Humans; Neoplasms; Satellite Viruses
PubMed: 24095032
DOI: 10.1016/j.jfma.2013.09.001 -
Cold Spring Harbor Perspectives in... Nov 2014HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to complete its life cycle. Two major specific patterns of infection have been described: the... (Review)
Review
HDV is a defective RNA pathogen requiring the simultaneous presence of HBV to complete its life cycle. Two major specific patterns of infection have been described: the coinfection with HDV and HBV of a susceptible, anti-HBs-negative individual, or the HDV superinfection of a chronic HBV carrier. Coinfection mostly leads to the eradication of both agents, whereas the majority of patients with HDV superinfection evolve to chronic HDV infection and hepatitis. Chronic HDV infection worsens the preexisting HBV-related liver damage. HDV-associated chronic liver disease (chronic hepatitis D) is characterized by necroinflammation and the relentless deposition of collagen culminating, within a few decades, into the development of cirrhosis and hepatocellular carcinoma.
Topics: Coinfection; Disease Progression; Hepatitis B; Hepatitis D; Hepatitis D, Chronic; Hepatitis Delta Virus; Humans; Superinfection
PubMed: 25368018
DOI: 10.1101/cshperspect.a021550 -
Cold Spring Harbor Perspectives in... Aug 2015Entry of hepatitis B (HBV) and hepatitis D viruses (HDV) into a host cell represents the initial step of infection. This process requires multiple steps, including the... (Review)
Review
Entry of hepatitis B (HBV) and hepatitis D viruses (HDV) into a host cell represents the initial step of infection. This process requires multiple steps, including the low-affinity attachment of the virus to the cell surface, followed by high-affinity attachment to specific receptor(s), and subsequent endocytosis-mediated internalization. Within the viral envelope, the preS1 region is involved in receptor binding. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as an entry receptor of HBV and HDV by affinity purification using a preS1 peptide. NTCP is mainly or exclusively expressed in the liver, and this membrane protein is at least one of the factors determining the narrow species specificity and hepatotropism of HBV and HDV. However, there are likely other factors that mediate the species and tissue tropism of HBV. This review summarizes the current understanding of the mechanisms of HBV/HDV entry.
Topics: Female; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Male; Receptors, Virus; Species Specificity; Taurocholic Acid; Tropism; Viral Envelope Proteins; Virion; Virus Internalization
PubMed: 26238794
DOI: 10.1101/cshperspect.a021378 -
Annual Review of Virology Sep 2021Despite their simplicity, viruses exhibit certain types of social interactions. Situations in which a given virus achieves higher fitness in combination with other...
Despite their simplicity, viruses exhibit certain types of social interactions. Situations in which a given virus achieves higher fitness in combination with other members of the viral population have been described at the level of transmission, replication, suppression of host immune responses, and host killing, enabling the evolution of viral cooperation. Although cellular coinfection with multiple viral particles is the typical playground for these interactions, cooperation between viruses infecting different cells is also established through cellular and viral-encoded communication systems. In general, the stability of cooperation is compromised by cheater genotypes, as best exemplified by defective interfering particles. As predicted by social evolution theory, cheater invasion can be avoided when cooperators interact preferentially with other cooperators, a situation that is promoted in spatially structured populations. Processes such as transmission bottlenecks, organ compartmentalization, localized spread of infection foci, superinfection exclusion, and even discrete intracellular replication centers promote multilevel spatial structuring in viruses.
Topics: Genotype; Virion; Virus Replication; Viruses
PubMed: 34242062
DOI: 10.1146/annurev-virology-091919-071712 -
Viruses Dec 2022Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA... (Review)
Review
Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.
Topics: Humans; Antiviral Agents; Influenza Vaccines; Defective Interfering Viruses; Defective Viruses; COVID-19; SARS-CoV-2; Orthomyxoviridae; Virus Replication
PubMed: 36560777
DOI: 10.3390/v14122773 -
Journal of Virology Nov 2021Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the...
Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the immunity induced by their parents to reach higher loads. We tested this by coinfecting mice with attenuated mutants of murid herpesvirus 4 (MuHV-4). Infection by the natural olfactory route routinely allowed mutant viruses to reconstitute wild-type genotypes and reach normal viral loads. Lung coinfections rescued much less well. Attenuated murine cytomegalovirus mutants similarly showed recombinational rescue via the nose but not the lungs. These infections spread similarly, so route-specific rescue implied that recombination occurred close to the olfactory entry site. Rescue of replication-deficient MuHV-4 confirmed this, showing that coinfection occurred in the first encountered olfactory cells. This worked even with asynchronous inoculation, implying that a defective virus can wait here for later rescue. Virions entering the nose get caught on respiratory mucus, which the respiratory epithelial cilia push back toward the olfactory surface. Early infection was correspondingly focused on the anterior olfactory edge. Thus, by concentrating incoming infection into a small area, olfactory entry seems to promote functionally significant recombination. All organisms depend on genetic diversity to cope with environmental change. Small viruses rely on frequent point mutations. This is harder for herpesviruses because they have larger genomes. Recombination provides another means of genetic optimization. Human herpesviruses often coinfect, and they show evidence of past recombination, but whether this is rare and incidental or functionally important is unknown. We showed that herpesviruses entering mice via the natural olfactory route meet reliably enough for recombination routinely to repair crippling mutations and restore normal viral loads. It appeared to occur in the first encountered olfactory cells and reflected a concentration of infection at the anterior olfactory edge. Thus, natural host entry incorporates a significant capacity for herpesvirus recombination.
Topics: Animals; Herpesviridae; Herpesviridae Infections; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Nose; Olfactory Mucosa; Open Reading Frames; Receptors, Odorant; Recombination, Genetic; Rhadinovirus; Virus Internalization
PubMed: 34523965
DOI: 10.1128/JVI.01555-21 -
International Journal of Molecular... Mar 2022Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in... (Review)
Review
Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses-hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis.
Topics: Cholesterol; Hepacivirus; Hepatitis A; Hepatitis B virus; Hepatitis C; Hepatitis Delta Virus; Hepatitis E virus; Hepatitis Viruses; Hepatitis, Viral, Human; Humans; Inflammation; Lipid Metabolism; Liver Cirrhosis
PubMed: 35409259
DOI: 10.3390/ijms23073897 -
Journal of Virology Aug 2021Ebola virus (EBOV), of the family , is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes...
Ebola virus (EBOV), of the family , is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissue samples using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV), or Marburg virus (MARV). Multiple 5' copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infections, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using reverse transcriptase PCR (RT-PCR) and deep sequencing, we also confirmed the presence of 5' cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection and that further study will lead to a better understanding of EBOV pathogenesis. The study of filovirus pathogenesis is critical for understanding the consequences of infection and for the development of strategies to ameliorate future outbreaks. Defective viral genomes (DVGs) have been detected during EBOV infections ; however, their presence in infections remains unknown. In this study, DVGs were detected in samples collected from EBOV- and SUDV-infected nonhuman primates (NHPs). The accumulation of these DVGs in the trailer region of the genome during infection indicates a potential role in EBOV and SUDV pathogenesis. In particular, the presence of DVGs in the testes of infected NHPs requires further investigation as it may be linked to the establishment of persistence.
Topics: Animals; Defective Viruses; Ebolavirus; Female; Genome, Viral; Hemorrhagic Fever, Ebola; Host-Pathogen Interactions; Macaca mulatta; Male; Virus Replication
PubMed: 34160256
DOI: 10.1128/JVI.00714-21 -
Viruses Dec 2022The genomes of RNA viruses may be monopartite or multipartite, and sub-genomic particles such as defective RNAs (D RNAs) or satellite RNAs (satRNAs) can be associated... (Review)
Review
The genomes of RNA viruses may be monopartite or multipartite, and sub-genomic particles such as defective RNAs (D RNAs) or satellite RNAs (satRNAs) can be associated with some of them. D RNAs are small, deletion mutants of a virus that have lost essential functions for independent replication, encapsidation and/or movement. D RNAs are common elements associated with human and animal viruses, and they have been described for numerous plant viruses so far. Over 30 years of studies on D RNAs allow for some general conclusions to be drawn. First, the essential condition for D RNA formation is prolonged passaging of the virus at a high cellular multiplicity of infection (MOI) in one host. Second, recombination plays crucial roles in D RNA formation. Moreover, during virus propagation, D RNAs evolve, and the composition of the particle depends on, e.g., host plant, virus isolate or number of passages. Defective RNAs are often engaged in transient interactions with full-length viruses-they can modulate accumulation, infection dynamics and virulence, and are widely used, i.e., as a tool for research on -acting elements crucial for viral replication. Nevertheless, many questions regarding the generation and role of D RNAs in pathogenesis remain open. In this review, we summarise the knowledge about D RNAs of plant viruses obtained so far.
Topics: Animals; Humans; RNA, Viral; Plant Viruses; RNA Viruses; RNA, Satellite; Virus Replication; Defective Viruses
PubMed: 36560818
DOI: 10.3390/v14122814 -
Pathogens and Disease Jul 2014In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These... (Review)
Review
In nature, vector-borne flaviviruses are persistently cycled between either the tick or mosquito vector and small mammals such as rodents, skunks, and swine. These viruses account for considerable human morbidity and mortality worldwide. Increasing and substantial evidence of viral persistence in humans, which includes the isolation of RNA by RT-PCR and infectious virus by culture, continues to be reported. Viral persistence can also be established in vitro in various human, animal, arachnid, and insect cell lines in culture. Although some research has focused on the potential roles of defective virus particles, evasion of the immune response through the manipulation of autophagy and/or apoptosis, the precise mechanism of flavivirus persistence is still not well understood. We propose additional research for further understanding of how viral persistence is established in different systems. Avenues for additional studies include determining whether the multifunctional flavivirus protein NS5 has a role in viral persistence, the development of relevant animal models of viral persistence, and investigating the host responses that allow vector-borne flavivirus replication without detrimental effects on infected cells. Such studies might shed more light on the viral-host relationships and could be used to unravel the mechanisms for establishment of persistence.
Topics: Animals; Carrier State; Disease Models, Animal; Flavivirus; Flavivirus Infections; Host-Pathogen Interactions; Humans
PubMed: 24737600
DOI: 10.1111/2049-632X.12178