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Viruses Apr 2022Integrase is the retroviral protein responsible for integrating reverse transcripts into cellular genomes. Co-packaged with viral RNA and reverse transcriptase into... (Review)
Review
Integrase is the retroviral protein responsible for integrating reverse transcripts into cellular genomes. Co-packaged with viral RNA and reverse transcriptase into capsid-encased viral cores, human immunodeficiency virus 1 (HIV-1) integrase has long been implicated in reverse transcription and virion maturation. However, the underlying mechanisms of integrase in these non-catalytic-related viral replication steps have remained elusive. Recent results have shown that integrase binds genomic RNA in virions, and that mutational or pharmacological disruption of integrase-RNA binding yields eccentric virion particles with ribonucleoprotein complexes situated outside of the capsid shell. Such viruses are defective for reverse transcription due to preferential loss of integrase and viral RNA from infected target cells. Parallel research has revealed defective integrase-RNA binding and eccentric particle formation as common features of class II integrase mutant viruses, a phenotypic grouping of viruses that display defects at steps beyond integration. In light of these new findings, we propose three new subclasses of class II mutant viruses (a, b, and c), all of which are defective for integrase-RNA binding and particle morphogenesis, but differ based on distinct underlying mechanisms exhibited by the associated integrase mutant proteins. We also assess how these findings inform the role of integrase in HIV-1 particle maturation.
Topics: HIV Integrase; HIV Integrase Inhibitors; HIV-1; Humans; RNA, Viral
PubMed: 35632668
DOI: 10.3390/v14050926 -
Current Opinion in Virology Dec 2018Particles containing degenerate forms of the viral genome which interfere with virus replication and are non-replicative per se are known as defective interfering... (Review)
Review
Particles containing degenerate forms of the viral genome which interfere with virus replication and are non-replicative per se are known as defective interfering particles (DIPs). DIPs are likely to be produced upon infection by any virus in vitro and in nature. Until recently, roles of these non-viable particles as members of a multi-component viral system have been overlooked. In this review, we cover the most recent studies that shed light on critical roles of DIPs during the course of infection, including: the modulation of virus replication, innate immune responses, disease outcome and virus persistence, as well as the evolution of the viral population. Together, these reports allow us to conceive a more complete picture of the virion population, and highlight the fact that DIPs are not a negligible subset of this population but instead can greatly influence the fate of infection.
Topics: Defective Viruses; Evolution, Molecular; Genetics, Population; Population Dynamics; Virus Replication; Viruses
PubMed: 30099321
DOI: 10.1016/j.coviro.2018.07.014 -
Viruses Oct 2021A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also... (Review)
Review
A substantial number of humans are at risk for infection by vector-borne flaviviruses, resulting in considerable morbidity and mortality worldwide. These viruses also infect wildlife at a considerable rate, persistently cycling between ticks/mosquitoes and small mammals and reptiles and non-human primates and humans. Substantially increasing evidence of viral persistence in wildlife continues to be reported. In addition to in humans, viral persistence has been shown to establish in mammalian, reptile, arachnid, and mosquito systems, as well as insect cell lines. Although a considerable amount of research has centered on the potential roles of defective virus particles, autophagy and/or apoptosis-induced evasion of the immune response, and the precise mechanism of these features in flavivirus persistence have yet to be elucidated. In this review, we present findings that aid in understanding how vector-borne flavivirus persistence is established in wildlife. Research studies to be discussed include determining the critical roles universal flavivirus non-structural proteins played in flaviviral persistence, the advancement of animal models of viral persistence, and studying host factors that allow vector-borne flavivirus replication without destructive effects on infected cells. These findings underscore the viral-host relationships in wildlife animals and could be used to elucidate the underlying mechanisms responsible for the establishment of viral persistence in these animals.
Topics: Animals; Animals, Wild; Central Nervous System Viral Diseases; Culicidae; Disease Vectors; Flavivirus; Flavivirus Infections; Host-Pathogen Interactions; Humans; Insect Vectors; Mosquito Vectors; Ticks
PubMed: 34696529
DOI: 10.3390/v13102099 -
The New Microbiologica Jul 2022The hepatitis D virus (HDV) is unique in animal virology. It is the smallest of human pathogens, re- quires the HBsAg capsid of the hepatitis B virus (HBV) to assembly...
The hepatitis D virus (HDV) is unique in animal virology. It is the smallest of human pathogens, re- quires the HBsAg capsid of the hepatitis B virus (HBV) to assembly into infectious virions, and parasitizes the transcriptional machinery of the host. Hepatitis D is ubiquitous but prevalence varies throughout the world. It is the most severe form of chronic viral liver disorder. Vaccination against the HBV has decreased the circulation of HDV in industrialized countries but Hepatitis D remains a significant medical issue in many areas of the developing world.
Topics: Animals; Hepatitis A; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; RNA, Viral
PubMed: 35920869
DOI: No ID Found -
Cold Spring Harbor Perspectives in... Nov 2015This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the... (Review)
Review
This work reviews specific related aspects of hepatitis delta virus (HDV) reproduction, including virion structure, the RNA genome, the mode of genome replication, the delta antigens, and the assembly of HDV using the envelope proteins of its helper virus, hepatitis B virus (HBV). These topics are considered with perspectives ranging from a history of discovery through to still-unsolved problems. HDV evolution, virus entry, and associated pathogenic potential and treatment of infections are considered in other articles in this collection.
Topics: Hepatitis D; Hepatitis Delta Virus; Humans; Virus Assembly; Virus Replication
PubMed: 26525452
DOI: 10.1101/cshperspect.a021568 -
Viruses Jan 2023Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination... (Review)
Review
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
Topics: Humans; Hepatitis Viruses; Hepatitis A; Hepatitis C; Hepatitis B; Hepatitis B virus; Hepatitis A virus; Hepatitis Delta Virus; Vaccines
PubMed: 36680254
DOI: 10.3390/v15010214 -
Chinese Medical Journal Apr 2022Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular... (Review)
Review
Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epidemiology, clinical feature, treatment, and prevention. We not only highlighted the remaining challenges but also the opportunities that can move the field forward.
Topics: Carcinoma, Hepatocellular; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Liver Cirrhosis; Liver Neoplasms
PubMed: 35234694
DOI: 10.1097/CM9.0000000000002011 -
Viruses Apr 2021Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the... (Review)
Review
Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pathogenesis varies and depends on the mode of HDV and HBV infection; a simultaneous HDV and HBV infection will lead to an acute hepatitis that will resolve spontaneously in the majority of patients, whereas an HDV super-infection of a chronic HBV carrier will mainly result in the establishment of a chronic HDV infection that may progress towards cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC). With this review, we aim to unravel Ariadne's thread into the labyrinth of acute and chronic HDV infection pathogenesis and will provide insights into the complexity of this exciting topic by detailing the different players and mechanisms that shape the clinical outcome.
Topics: Animals; Carcinoma, Hepatocellular; Coinfection; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis Delta Virus; Hepatitis delta Antigens; Humans; Liver Neoplasms; Mice; RNA, Viral; Satellite Viruses; Virus Replication
PubMed: 33924806
DOI: 10.3390/v13050778 -
Cold Spring Harbor Perspectives in... Jan 2016Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of... (Review)
Review
Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus. The identification of hepatitis B viruses (HBVs) in higher primates, such as chimpanzee, gorilla, orangutan, and gibbons that cluster with the human HBV, as well as a number of recombinant forms between humans and primates, further implies a more complex origin of this virus. We discuss the current theories of the origin and evolution of HBV and propose a model that includes cross-species transmissions and subsequent recombination events on a genetic backbone of genotype C HBV infection. The hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the HBV for the completion of its life cycle. The origins of this virus remain unknown, although some recent studies have suggested an ancient African radiation. The age of the association between HDV and HBV is also unknown.
Topics: Animals; Coinfection; Evolution, Molecular; Fossils; Genome, Viral; Hepadnaviridae; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Phylogeny; Recombination, Genetic; Zoonoses
PubMed: 26729756
DOI: 10.1101/cshperspect.a021360 -
Viruses Jul 2023Hepatitis delta virus (HDV) is the smallest known human virus and causes the most severe form of human viral hepatitis, yet it is still not fully understood how the... (Review)
Review
Hepatitis delta virus (HDV) is the smallest known human virus and causes the most severe form of human viral hepatitis, yet it is still not fully understood how the virus replicates and how it interacts with many host proteins during replication. This review aims to provide a systematic review of all the host factors currently known to interact with HDV and their mechanistic involvement in all steps of the HDV replication cycle. Finally, we discuss implications for therapeutic development based on our current knowledge of HDV-host protein interactions.
Topics: Humans; Hepatitis Delta Virus; Virus Replication
PubMed: 37515216
DOI: 10.3390/v15071530