Retroviruses Flashcards
What are retroviruses?
The Retroviridae are a family of enveloped (+) sense ssRNA viruses that replicate through a DNA intermediate using reverse transcriptase
What are retroviruses associaetd with?
Retroviruses are associated with cancers, leukemias and the AIDS syndrome, and cause degenerative and neurological syndromes
Give a brief history of retroviruses
- The first association of viruses with cancer was in early 1900’s with the discovery by Wilhelm Ellerman and Olaf Bang that leukemia could be transmitted from one chicken to another by injecting leukemia cell extracts
- In 1911 Peyton Rous showed that a bacterial free filtrate from solid tumors of chickens could cause an identical cancer in chickens inoculated with the filtrate
What is the Baltimore classification of viruses based on?
The mechanism of mRNA production
Retrovirus Classification table
Describe Retrovirus structure
Retrovirus virions are 80-120 nm in diameter, have spherical morphology, a phospholipid envelope with knobs
Describe the Retrovirus genome
- RNA genome is diploid
- 2 copies of a 7-10kb ssRNA, capped and polyadenylated
- both RNAs are joined near their 5’ ends by hydrogen bonds
- looks like mRNA, but does not serve as mRNA immediately after infection
- encode at least 4 genes called gag, pro, pol and env
Retroviral proteins: pro
- pro gene encodes a protease PR
- Required for processing of Gag polyprotein into MA, CA, NC
- pro gene can be encoded separately or as part of Gag or Gag-Pro-Pol polyprotein
Retroviral proteins: gag
gag (group-specific antigen) protein is proteolytically processed into:
- MA (matrix)
- CA (capsid)
- NC (nucleocapsid), around 2000 copies, binds to and encloses RNA
Retroviral proteins: pol
pol protein encodes enzymes
RT (Reverse Transcriptase)
- RNA-dependent DNA polymerase
- RNase H
- DNA-dependent DNA polymerase
IN (Integrase)
- The retrovirus DNA is inserted at random into the host genome. If it is inserted into oncogenes retroviruses can convert normal cells into cancer cells.
Retroviral proteins: env
env protein encodes:
- SU (surface glycoprotein)
- TM (transmembrane protein)
State the Retroviral replication cycle
- Attachment (adsorbtion)
- Penetration (entry, uncoating)
- Synthesis
- Reverse transcription
- Integration into host cell genome (provirus)
- Viral genome replication (transcription) and viral protein synthesis
- Assembly (maturation, packaging)
- Release (budding)
Show the Retroviral replication cycle
Explain the Retroviral replication cycle
- Retroviruses penetrate either by fusion with the PM, or via endocytosis
- Integration is essential for productive infection
- Transfer of DNA to nucleus happens during cell division (simple retroviruses), when nuclear envelope is disassembled
- Provirus is stable; no mechanism for precise excision is known; integration is essentially irreversible
- Most/simple retroviruses do not kill the host cell, but establish a persistent infection ® the host cell survives and produces low levels of virus indefinitely
- Retrovirus acquires its envelope by budding through the plasma membrane.
SU and TM are incorporated into the virion during budding.
Explain Endogenous retroviruses
- Eukaryotic genomes contain a very large number of genetic elements that are related to retroviral genomes
- Retrotransposons encode RT and can move around within the genome by a process that uses RT and insertion (similar to retroviruses) related to retroviruses, but have no independent lives as viruses
- Around 42% of the human genome is made up of retrotransposons
