Viral Pathogens :Classification ,Biology -Diseases 1 Flashcards
What are the different types of viruses?
Tobacco mosaic virus
Adenovirus
Influenza virus
Bacteriophage T4
How do we classify viruses?
Not by structure but rather through genomes : Single-stranded RNA (ssRNA) Double stranded RNA (dsRNA) Single stranded DNA (ssDNA ) Double stranded RNA (dsDNA)
Double stranded genomes contain 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
They can be linear /circular
It can have one genome or segmented
Genomes can encode information(genes ) in positive or negative sense
What is the central DOGMA
This is the process through which proteins can be created from DNA bouble strand .
How can viruses use the central dogma ?
There are DNA viruses which replicate DNA , RNA virus which create RNA or retroviruses which can create both.
All produce proteins
Outline the baltimore classification
This is how viruses are grouped .
It contains information of genome types and how they are replicated .
Produce RNA which produces proteins
What does HIV look like ?
Nucleic acid surrounded by protein
Two copies of RNA , covered by protein and then membrane.
Glycoproteins stick out of the membrane (envelope proteins )
Enzymes found in HIV :
Protease
Integrase
Reverse transcriptase
Outline the structure of a mature HIV-1 particle
Outer envelope of HIV consists of a lipid bilayer with protruding ENV spikes (heterodimers of SU3TM3)
Inside the envelope lie shells of Gag proteins.
In the immature particle Gag itself forms a single shell.
Ma associates with the membrane CA forms the conical capsid NC coats the viral RNA genome.
The core contains two genomic RNA strands(plus strand)
tRNA and aprox 50 copies of d IN)
Outline the genome organisation of Retroviruses
HIV has the same genome structure ,long stranded R NA from which we can produce different polyproteins through alternative splicing , transcriptional frame shift
To make the proteins three polyproteins are required:
Synthesise 3 polyproteins
Gag which produces (group specific antigen );viral core proteins ; MA (matrix) , Ca(Capsid) and NC (nucleocapsid)
NC (Nucleocapsid)
Pol: Viral enzymes
protease (PR), reverse transcreiptase (RT) and integrase (IN)
Env; envelope glycoprotein gp120 SU (surface );gp41 TM (Transmembrane)
Outline retroviral entrance into the cell
This entrance requires the engagement of the viral envelope proteins with cellular receptors which allows the virus to attach and fuse into the cell cytoplasm.
Describe and outline HIVs envelope proteins
HIV envelope (spike proteins) consists of trimer of transmembrane subunits (gp10 peptide subunits & gp120 peptide subunits) and is covered with glycans.
Glycans are a post-translational modification.
What are glycans ?
Sugar-based polymers that coat cells and decorate most proteins, forming glycoproteins.
What is the mechanism of HIV-1 entry into the cell ?
It requires two membrane proteins : CD4 and a chemokine receptor (CCR5/CXR4)
Native trimer
These are the native trimers of the virus searching for cell surface receptor.
The gp120 is tucked into conformation called native.
.CD4 binding site exposure
CD4 recognises a sequence /structure within surface subunit of HIV ( gp120) of envelope.
Fusion peptide insertion
Following the surface subunit engages with CD4 this causes a conformational change in the envelope protein and becomes a open conformation
The open conformation will uncover the transmembrane subunits
HIV will also recognise a co receptor. The interaction between surface subunit with co-receptor stimulates the transmembrane region to go into cell membrane.
Insert transmembrane domain and surface subunit into lipid bilayer and this will form 6-Helix Bundle Formation
Membrane fusion.
Envelope trimers are three copies of transmembrane.
HIV is tropic for CD4 expressing cells such as helper T cells and macrophages; the loss of which results in immunodeficiency (& AIDS)
Outline the early phases of HIV-1 infection
Following fusion:
The virus enters the cell and needs to move to site of replication.
This is the area which the replication genome will most favour.
The HIV virus wants to replicate in the nucleus mostly.
-To use the cells machinery to multiply
Following fusion , it utilises the cell microtubule network to carry the core containing the genome to the nuclear membrane.
What are some different methods of nuclear entry pathways of HIV genome core
Typically , the Viral core containing the viral RNA genome has capsid modifications
What happens once the virus reaches the nucleus ?
Reverse transcriptase is used for reverse transcription.
RNA to DNA
RNA is in the capsid , reverse transcriptase enzyme will mediate the production of DNA