Influenza

Negative-strand RNA virus that contains 8 pieces of ssRNA

1) Entry into cell and release of minus (­) strands

2) Production of plus (+) strand to get dsRNA. Requires an RNA replicase that's packaged in the virion along with the ssRNA strands

3) ­ strands are used as templates for mRNA (+ strand) synthesis

4) + strands are used as templates for viral genome (­ strand) synthesis

5) Production of viral capsid proteins

6) Assembly of new virions

High genetic variation in flu viruses because:

1) Can mix up the 8 pieces from different viruses. Called viral reassortment and can occur if have mixed infection (e.g. porcine virus and human virus both infect pig).

2) RNA mutates more frequently than DNA because RNA replicase, just like RNA polymerase, has virtually no proofreading ability.

Influenza A virus first was an avian virus that left the original host (ducks) then moved to swine and horses then humans.

Other negative strand RNA viruses are measles, mumps and Ebola. Ebola may be too lethal to be an effective disease agent because often kills the host before it can move to a new host.

 

Retroviruses

ssRNA plus strand but not used as mRNA

1) Entry into host cell

2) Dissociation of two identical plus (+) RNA strands that are bound to two tRNAs from the last host

3) Reverse transcriptase (the protein is packaged in the virion) uses the tRNA bound to the ssRNA (binds at the primer binding site in the LTR) as a primer for DNA synthesis and makes one strand of DNA to form a DNA:RNA hybrid

4) Most of the RNA strand is degraded, but a small fragment is left as a primer for reverse transcriptase

5) Second DNA strand is made by reverse transcriptase

6) dsDNA is integrated into host nuclear chromosome

7) Transcription of provirus produces plus (+) RNA strands that are capped and tailed just like normal mRNA, then transported out of the nucleus where they can be packaged into virions with a few molecules of reverse transcriptase

Virion contains an actual mRNA that has a cap and a tail, but it's not used as a mRNA

 

HIV

Infects T cells and brain cells

Attaches to T cells CD4 receptors on surface of T cells via a viral protein called gp120. Once integrated into the host chromosome, produces gp120 protein that's expressed at the cell surface of the infected T cell. This causes the infected T cell to attach to uninfected T cells by the interaction of the gp120 protein with the CD4 receptors on the healthy cells. Once the T cells are clumped together, they soon die. AIDS patients are therefore immunocompromised and often succumb to opportunistic diseases.

AZT (azidothymidine) is a base analog of thymidine that gets incorporated into the DNA made during reverse transcription. AZT lacks a 3' OH group so the DNA strand can't be extended. Also affects host DNA synthesis, especially in bone marrow. But AZT not really effective because HIV mutates so often so can get AZT resistant viruses.

 

Prions

Infectious proteins

Produced from normal host gene. Once made, may fold into bad form. Bad protein forms can cause the good proteins to fold into the bad conformation.

Causes scrapie in sheep, mad cow disease, mink encephalopathy and kuru. All caused by eating raw brains of infected organisms.


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Last updated: 9-April-98 / laa