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Herpes simplex virus co-infection facilitates rolling circle replication of the adeno-associated virus genome. 2021

Anita Felicitas Meier, and Kurt Tobler, and Remo Leisi, and Anouk Lkharrazi, and Carlos Ros, and Cornel Fraefel
Institute of Virology, University of Zurich, Zurich, Switzerland.

Adeno-associated virus (AAV) genome replication only occurs in the presence of a co-infecting helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1). AdV5-supported replication of the AAV genome has been described to occur in a strand-displacement rolling hairpin replication (RHR) mechanism initiated at the AAV 3' inverted terminal repeat (ITR) end. It has been assumed that the same mechanism applies to HSV-1-supported AAV genome replication. Using Southern analysis and nanopore sequencing as a novel, high-throughput approach to study viral genome replication we demonstrate the formation of double-stranded head-to-tail concatemers of AAV genomes in the presence of HSV-1, thus providing evidence for an unequivocal rolling circle replication (RCR) mechanism. This stands in contrast to the textbook model of AAV genome replication when HSV-1 is the helper virus.

UI MeSH Term Description Entries
D010322 Parvoviridae Infections Virus infections caused by the PARVOVIRIDAE. Parvovirus Infections,Infections, Parvoviridae,Infections, Parvovirus,Infection, Parvoviridae,Infection, Parvovirus,Parvoviridae Infection,Parvovirus Infection
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006378 Helper Viruses Viruses which enable defective viruses to replicate or to form a protein coat by complementing the missing gene function of the defective (satellite) virus. Helper and satellite may be of the same or different genus. Helper Virus,Virus, Helper,Viruses, Helper
D006561 Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.) Herpes Simplex Virus Infection
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000229 Dependovirus A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2. Adeno-Associated Viruses,Dependoparvovirus,Adeno-Associated Virus,Virus, Adeno-Associated,Viruses, Adeno-Associated,Adeno Associated Virus,Adeno Associated Viruses,Dependoparvoviruses,Dependoviruses,Virus, Adeno Associated,Viruses, Adeno Associated
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D016679 Genome, Viral The complete genetic complement contained in a DNA or RNA molecule in a virus. Viral Genome,Genomes, Viral,Viral Genomes
D060085 Coinfection Simultaneous infection of a host organism by two or more pathogens. In virology, coinfection commonly refers to simultaneous infection of a single cell by two or more different viruses. Mixed Infection,Co-infection,Polymicrobial Infection,Secondary Infection,Secondary Infections,Co infection,Co-infections,Coinfections,Infection, Mixed,Infection, Polymicrobial,Infection, Secondary,Infections, Mixed,Infections, Polymicrobial,Infections, Secondary,Mixed Infections,Polymicrobial Infections

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