Question

Herpes and adenoviruses are both viruses with linear double stranded DNA-gemones, but their replication mechanism differ considerably. Give step by step-summaries of both mechanisms (you may use drawings). Note. the question refers to replication mechanism and not life cycle.

Answer 1

# Replication mechanism of Herpes virus :-
*Invasion of cells by HSV1 requires binding of the envelope gC (glyco-protein-C) and/or gB to Heparan sulfate receptors, engagement by gD of one of several co-receptors including HveA (Herpes virus entry mediator A, also known as HVEM, Herpes Virus Entry Mediators), fusion of the viral envelope with the cell plasma membrane and delivery of the viral capsid into the cell cytoplasm.
*Along with the capsid viral proteins VHS and VP16 are also released in the cytoplasm.
*The incoming viral capsids are subsequently propelled to nucleopore for entry in the nucleus where it gets disintegrated and only DNA is released into the nucleus.
*The viral genome is uncoated for viral transcription and replication in the nucleoplasm.
*There are two main phases of transcription–early, which takes place prior to genome replication, and late, which takes place upon replicated genomes in virus replication compartments formed in the infected cell nucleus.
*Three distinct classes of mRNAs are made: Alpha, Beta, and Gamma which are regulated in a coordinated, cascade fashion.
*The Alpha or IE (Immediate-early) genes contain the major transcriptional regulatory proteins and their production is required for the transcription of the Beta and Gamma gene classes.
*The Beta proteins include the enzymes that are required for replication of the viral genome: a DNA polymerase, a single-strand DNA-binding protein, a primosome or helicase-primase, an origin-binding protein, and a set of enzymes involved in DNA repair and in deoxynucleotide metabolism.
*Viral DNA synthesis begins shortly after the appearance of the Beta proteins and the temporal program of viral gene expression ends with the appearance of the Gamma or late proteins, which constitute the structural proteins of the virus.
*The linear 153Kb pair genome circularizes shortly after infection of susceptible host cells and then enters a rolling circle mode of DNA replication generating branched concatameric DNA, which is then cleaved to release linear ds DNA.
*Viral transcription and DNA replication occurs in the nucleus; the particle assembles and exits from epithelial cells in the skin causing a primary infection.
*The virion acquires its envelope by budding through the nuclear membrane.

Replication mechanism of Adenovirus :-

Adenovirus replicates inside the nucleus. By the DNA replication process, the adenovirus multiplication cycle is separated into two phases i.e., an early phase and a late phase.
#Step I: Attachment and entry
*Adenovirus attaches to the host cell via its fiber structure to Coxsackie and Adenovirus receptor (CAR) receptor on host cell.
*The attachment of fiber to its receptor on host cell is followed by interaction of penton base with cellular integrin which promote receptor mediated internalization.
#Step II: Uncoating
*The virus is internalized into clathrin coated endosome and the high pH of endosome helps in uncoating of virus
*Transport of viral DNA into nucleus
*The viral nucleocapsid is transported from cytosol to nucleus by the help of microtubules.
#Step III: Early Transcription
*It is the early event in viral replication, and occurs before viral DNA synthesis begins.
*It is the preparatory phase in which transcription of viral DNA occurs to mRNA (early transcript).
*Early transcript undergoes translation to produce about 20 different early proteins. These early proteins induces host cell to enter into S-phase of cell cycle and to create condition favorable for viral replication.
#Step IV: DNA replication
*Viral DNA replication takes place in nucleus.
*The viral encoded protein at 5’ end of viral DNA strand acts as primer for initiation of viral DNA synthesis.
*Late event begins concomitantly with onset of viral DNA synthesis.
#Step V: Late Transcription and translation
*A large single primary transcript is synthesized from virus DNA which spliced into 18 fragments and each fragment acts as mRNA and are transported to cytoplasm.
*In the cytoplasm, translation occurs and viral structural proteins are synthesized.
#Step VI: Viral morphogenesis and release
*Morphogenesis of Adenovirus occurs inside nucleus.
*Viral DNA then gets packaged into preformed capsid forming mature virus particle.
*Mature virus particles are stable, infectious and resistant to nuclease enzyme of host cell.
*Adenovirus infection does not lyse the host cell.
*Mature virus is then release from host cell by budding.