L3 - Viral Pathogens 1 Flashcards
What are the different types of viruses?
- RNA viruses
- DNA viruses
- viruses covered by protein coat
- viruses covered by protein coat and membrane
What are the different structures of viral genomes?
Single-stranded RNA (ssRNA)
Double-stranded RNA (dsRNA)
Single-stranded DNA (ssDNA)
Double-stranded RNA (dsDNA)
Double-stranded genomes have complementary base pairing
RNA genomes can be linear and segmented i.e. more than one RNA per capsid
DNA genomes can be linear or circular.
How do viruses use central dogma?
use central dogma to create viral proteins needed for replication.
DNA polymerase = DNA replication
RNA polymerase = DNA to RNA
ribosomes = RNA to protein
What is the Baltimore classification of viruses?
system that classifies viruses based on their way of mRNA synthesis
group 1 - dsDNA group 2 - ssDNA group 3 - dsRNA group 4 - +ssRNA group 5 - -ssRNA group 6 - +ssRNA-RT group 7 - dsDNA-RT
Describe how HIV looks?
2 copies of RNA, covered by a layer of protein, covered by a layer of membrane. Protruding from the membrane, there are envelope glycoproteins (spikes).
Within the virus, there are also a number of viral enzymes like protease, integrase and reverse transcriptase.
What are Gag proteins on HIV?
they are major structural proteins (group specific antigen protein).
Made up of 3 parts:
- MA (matrix) associates with the membrane
- CA (caspid) forms the conical caspid
- NC (nuclear capsid) coats the viral genome
What 3 polyproteins do retroviruses synthesise, and what do they do?
Gag = viral core proteins (MA, CA, NC)
Pol = vira enzymes (PR, RT, IN)
Env = envelope glycoproteins (gp 120 SU, gp41 TM)
Describe the process whereby HIV binds to a host cell?
HIV surface subunit (GP120), engages a CD4 receptor on host cell membrane, a profound conformational change in the envelope protein of HIV.
Surface subunits of HIV moves into open conformation from native, and this uncovers transmembrane subunits.
During this process, HIV recognises co-receptor (CCR5).
Transmembrane subunits insert into lipid bilayer of host cells, which causes a 6-helix bundle formation/membrane fusion.
Envelope trimers from HIV (3 copies of TM), insert into bilayer which form helix bundle and pushes membrane apart.
Why is HIV trophic for CD4 expressing cells?
It cannot enter the cells without CD4 and co-receptor.
Can enter T-cells and macrophages
What does HIV do once it enters the host nucleus?
begins reverse transcriptase - turning RNA into DNA
Describe how the HIV DNA genome is integrated into the HOST genome?
viral linear DNA
at the end of those viral DNA, there are certain sequences.
The intergrase enzyme recognises those sequences at the terminals. It then binds the viral DNA and the cellular host DNA. It cuts the host DNA, and sticks the viral DNA into the space it made.
the 2 ends of the linear viral DNA are bought together in the intergrase enzyme, and makes a cut while bending the linear viral DNA around the cellular DNA. Once they are joined together, it is called a provirus
What cellular proteins are required for viral DNA integration into cellular DNA?
LEDGF/P75 which binds HIV integrase and facilitates targetting to chromatin
How does the HIV virus ensure that viral genes are given preferential treatment during transcription?
The viral Tat protein is produced from the genome first.
Tat protein specifically binds to TAR RNA (region on RNA that is needed for activation of viral promoter).
It therefore enhances the production of RNA and elonates RNA pol.
What is the REV protein and what is its function?
Virally encoded protein REV moves back into nucleus and binds to RRE region of viral RNA and causes the movement of viral RNA out of the nucleus, via the interaction with Crm1.
What is ESCRT machinery and what does it do?
it organises all the viral parts at the membrane before budding occurs
