REPLICATION OF DNA VIRUSES

General strategy—the virus must enter the cell. Once inside it must transcribe its genome, replicate its genome, make viral proteins, assemble progeny viruses. Then it must get out of the cell.

For DNA viruses, transcription occurs in the nucleus of the cell. Transcription factors are important for the early phase of transcription and can come from the host cell, the virus or both.
Temporal regulation—timing of DNA transciption. Most have their transcription broken up into early genes and late genes. Early genes get transcribed immediately after the viral DNA gets into the nucleus. These genes influence the viral-cell interactions.

Viruses use alternative splicing patterns to increase the diversity of their gene products from a small amount of DNA. Some process RNA and some temporally regulate their transcription.

Latency—in the world of molecular virologists had to do with the activity of the virus within in the cell—incorporation of the viral genome into the host in the case of retroviruses. In clinical terms it is the absence of clinical symptoms.

Parvovirus—

smallest DNA virus that requires growing cells (B19) or helper virus. They carry no baggage with them—they have barely enough to enter and execute a viral cycle. The reason they need growing cells—they are replicating DNA actively—the virus needs the machinery used for DNA replication. They don’t grow well inside of static cells but do well in the bone marrow and would not grow well in the heart or CNS.

B19—one of the viruses that grows in the bone marrow and causes anemia.

It has single stranded chromosome with inverted repeats at the end of the linear molecule that fold back and serve as primers for DNA replication. During repplication, you get both positive and negative strands.

The positive and negative strands both get incorporated into progeny phage. IT is a lytic bacteria and destroys the host cell at the end of the cycle.

Papovavirus—small icosahedral viruses. They have double stranded DNA about 8 kb.

• Non-covalent interactions hold the capsid together. There is temporal regulation of transcription. There are early, late and non-coding DNA.
• The non-coding regions may be regulatory regions, but don’t code for protein.
• Early genes are the genes needed first and late refers to genes transcribed later.
• The early genes code for T antigen—(transforming proteins) that have the capabitity to interact with the cell to change its growth—usually they promote mitosis.
• Cells infected with this kind of virus are neoplastic-like.
• MRNA initiation—origin or replication (bi-directional)—forms of non-coding regions.
• Late genes—VP—structural proteins—assebly occurs in the nucleus.
• SP40 virus—famous history because of its use in research of oncogenic properties of viruses. It infects monkeys.

Adenoviruses—

• icosadeltahedral virus with fibers. It causes gastrointestinal infections.
  
• It has a double stranded DNA chromosome that is linear with a 5’ terminal protein. It transcribes from both strands.
  
• Early genes are transcribed from four different promoters. -transactivator genes as E1A and E1B—proteins that are important for cell-virus interactions.
  
• These genes promote transformation. This makes them neoplastic like.
• There is a viral coded DNA polymerase. It also has late genes that uses one promoter. Rthis virus has the capability of having a lytic cycle or latent cycles—the virus can just hang out in the nucleus. The oncogenic cycle exists in which the cell becomes neoplastic.
• Splicing mechanisms are used to make a more diverse set of proteins from the genome.

Herpes viruses—large enveloped icosadeltahedral virions. This is a complex virus.

• They are large and enveloped! They have a linear double stranded DNA chromosome. 100 million base pairs. It has unique regions that can be bracketed by direct repeat regions (seen mainly in epstien barr) while the inverted repeats are more common in the HSV, VZV, and CMV—these inverted repeats allow them to recombine to make unique strains.
• Immediate early genes give rise to DNA binding factors—they sit on the genome and regulate the genome expression of the virus.
• Early genes—DNA polymerase. These viruses contain a lot of their own enzymes.
• Herpes can regulate its own transcription pattern and can drive itself into latency and this occurs in neurons mostly. In this stage, there is no DNA replication. This is a molecular latency.
• Late genes encode the structural proteins.
• Latency can be broken and we are not sure exactly how, but there are physiological states that can precipitate this action.
• HSV 6 and EB don’t make unique strains—lack inverted repeats.

Pox viruses—large complex viruses. They have linear double stranded DNA genomes. They are so large that they can be seen with light microscopy.

• All replication events occur in the cytoplasm. This is the only virus that does it here.
• They encode all the proteins for mRNA and DNA synthesis. DNA replicates in the cytoplasmic inclusions.
• This virus is usually lytic.

Hepadnavirus—hepatitis B virus. The other forms of hepatitis are RNA viruses.

• This is an enveloped virus that is unique in that it uses a reverse transcriptase. IT has a circular double stranded DNA.
  
• The genome is partially double stranded.
  
• It encodes a reverse transcriptase—DNA is replicated using RNA intermediate.
• There are overlapping mRNAs in the genome. 3500base mRNA is the template for the genome.
• RNA-dependent DNA polymerase (RT) that uses a large mRNA— RNAase H is used to get rid of the leftover RNA
• Integrated genome—found in hepatocellular CA—this could be the connection b/w the infection of HepB and cancer.

Category: Microbiology Notes