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Compare and contrast replication strategies of retroviruses, herpesviruses, adenovirus, poxvirus and parvovirus by addressing briefly how...

  1. Compare and contrast replication strategies of retroviruses, herpesviruses, adenovirus, poxvirus and parvovirus by addressing briefly how each of these viruses has solved the end replication problem and how each of these viruses primes DNA polymerization.
  1. Compare and contrast the entry strategies of retroviruses, picornaviruses and influenzaviruses. Identify features common to any of the viruses, and which features are unique due to specific elements of the virion.
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Retroviruses

(1) Entry into host cells,

(2) Reverse transcription of the RNA genome and generation of the double-strand proviral DNA,

(3) Integration of the proviral DNA into the host genome,

(4) Transcription of the viral genes from the 5′-LTR, splicing, and translation, and

(5) Production of viral particles. Integration of proviral DNA occurs only in dividing cells, and the integration site (only one per cell) is essentially random.

Herpesviruses

(1)HSV virion attaches to host cell with the envelope glycoprotein (gC) onto heparan sulfate moieties of cellular proteoglycans. Viral gD is believed to bind to a secondary cellular receptor.

(2) The viral envelope fuses to the plasma membrane in a pH-independent fashion such that the nucleocapsid enters the cytoplasm. gB, gD, and gH are instrumental glycoproteins for this phenomenon.

(3) The capsid travels along the cytoskeleton to a nuclear pore where the viral DNA is released. The linear genome enters the nucleus and circularizes.

(4) Once in the nucleus, the viral DNA is transcribed into mRNA by cellular RNA polymerase II. In herpesviruses, viral gene expression is tightly regulated and divided into 3 kinetic classes of expression.
* A tegument protein associates with 2 celluar proteins, and the complex transactivates transcription of HSV's five immediate-early (IE or alpha) genes. IE genes generally encode regulatory proteins.
* An IE protein initiates transcription of the early (E or beta) genes. These gene products are enzymes needed to increase the pool of nucleotides and for viral replication.
* Lastly, late (L or gamma) genes are activated for production of viral structural proteins.

(5) After transcription in the nucleus, all mRNA transcripts are translated into protein in the cytoplasm. Subsequently, the proteins can go to the nucleus, stay in the cytoplasm, or become a part of the membrane bilayer.

(6) Capsid proteins assemble in the nucleus to form empty capsids.

(7) Full-length viral DNA is packaged to form nucleocapsids.

(8) The nucleocapsids associate with segments of the nuclear membrane where tegument and glycosylated envelope proteins have bound. This association triggers envelopement by budding through the nuclear membrane.

(9) Enveloped virions accumulate in the endoplasmic reticulum (ER).

(10) Mature virions are released by exocytosis.

(11) Virus-specific proteins are also found on the plasma membrane of infected cells.

Adenovirus

The life cycle of an adenovirus is divided into early and late phases, separated by the DNA replication process. In the early phase, the virus attaches to a cell with its fibers. The penton base protein interacts with the host cell integrins, and the penton is internalized by the host cell through receptor-mediated endocytosis. The penton is disassembled as it is transported to the nucleus, where the viral particle releases its DNA. The viral DNA takes over as terminal protein attached to the end of the DNA strand initiates transcription. The early genes are responsible for making regulatory proteins, which alter the host proteins to prepare for DNA synthesis, activate other virus genes, and provide protection from the host's immune system. Viral DNA replication now occurs.

The late phase begins when the late genes are expressed during DNA replication. These genes produce proteins that are involved in virus particle assembly. The host's cellular processes are shut down as transport of mRNA to the cytoplasm is blocked when the late genes are expressed. Viral mRNA is transported to the cytoplasm and translated instead. Virus assembly occurs. Finally, the host cell dies due to a build-up of adenovirus death protein. As the cell dies, the new virus particles are released from the cell.

Poxvirus

The virus first binds to a receptor on the host cell surface; the receptors for the poxvirus are thought to be glycosaminoglycans. After binding to the receptor, the virus enters the cell where it uncoats. Uncoating of the virus is a two step process. Firstly the outer membrane is removed as the particle enters the cell; secondly the virus particle (without the outer membrane) fuses with the cellular membrane to release the core into the cytoplasm. The pox viral genes are expressed in two phases. The early genes encode the non-structural protein, including proteins necessary for replication of the viral genome, and are expressed before the genome is replicated. The late genes are expressed after the genome has been replicated and encode the structural proteins to make the virus particle. The assembly of the virus particle occurs in five stages of maturation that lead to the final exocytosis of the new enveloped virion. After the genome has been replicated, the immature virion assembles the A5 protein to create the intracellular mature virion. The protein aligns and the brick-shaped envelope of the intracellular enveloped virion. These particles are then fused to the cell plasma to form the cell-associated enveloped virion, which encounters the microtubules and prepares to exit the cell as an extracellular enveloped virion. The assembly of the virus particle occurs in the cytoplasm of the cell and is a complex process that is currently being researched to understand each stage in more depth. Considering the fact that this virus is large and complex, replication is relatively quick taking approximately 12 hours until the host cell dies by the release of viruses.

Parvovirus

To enter host cells, parvoviruses typically bind to a sialic acid-bearing cell surface receptor and penetration into the cytoplasm is mediated by a phospholipase A2 activity carried on the amino-terminal peptide of the capsid VP1 polypeptide.[3] Once in the cytoplasm, the intact virus is translocated into the nucleus prior to uncoating. Transcription only initiates when the host cell enters S-phase under its own cell cycle control, when the cell's replication machinery converts the incoming single strand into a duplex transcription template, allowing synthesis of mRNAs encoding the nonstructural proteins, NS1 and NS2. The mRNAs are transported out of the nucleus into the cytoplasm, where the host ribosomes translate them into viral proteins. Viral DNA replication proceeds through a series of monomeric and concatemeric duplex intermediates by a unidirectional strand-displacement mechanism that is mediated by components of the host replication fork, aided and orchestrated by the viral NS1 polypeptide. NS1 also transactivates an internal transcriptional promoter that directs synthesis of the structural VP polypeptides. Once assembled capsids are available, replication shifts from synthesizing duplex DNA to displacement of progeny single strands, which are typically negative-sense and are packaged in a 3'-to-5' direction into formed particles within the nucleus. Mature virions may be released from infected cells prior to cell lysis, which promotes rapid transmission of the virus, but if this fails, then the virus is released at cell lysis

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