3.2 viruses as pathogens Flashcards
what is tissue tropism? what influences it?
reflects the ability of a given pathogen to infect a specific organ or sets of organs
- Tissue tropism is heavily influenced by the presence of cellular receptors permitting the entry of the virus
what explains species susceptibility to certain viruses?
- Animal species express different receptors which explains species susceptibility to some viruses
what do viruses exploit to gain entry to a host cell?
-molecules on the surface of a host cell’s plasma membrane = receptors
what is the general molecular structure of a viral receptor?
can be proteins, glycoprotein, carbohydrate, or lipid
how does a virus attach to the membrane of a host cell? How does this work with influenza, for example?
- Viral surface proteins/glycoproteins (ligands) interact with
receptors/co-receptors on the surface of host cells
*Viruses interact with the cellular receptor in a lock-and-key
manner - Influenza hemagglutinin (LIGAND) interacts with sialic acid linked glycoproteins on host cells (RECEPTOR)
what determines the mechanism of virus entry into the host cell?
the nature of the receptor
what mechanisms of entry into the host cell might a virus use?
-Direct penetration where a viral protein forms a pore to release its genome
-Receptor mediated endocytosis of all non-enveloped viruses and some enveloped viruses
-Fusion between the viral protein of enveloped viruses and the cell membrane
what mediates virus-cell fusion? where does it occur and at what pH?
- Virus-cell fusion is mediated by one or more surface glycoproteins of the mature virion envelope.
- Fusion can occur at the cell surface at neutral pH or within an endosomal compartment at low pH.
how does a viral fusion protein normally exist? What happens when it gets triggered?
- The fusion protein exist in a ‘native’ fusion-competent state, which is most often, but not always, metastable.
- Following triggering (low pH, interaction with receptors, enzymatic cleavage by proteases), the fusion protein undergoes conformational changes allowing the fusion peptide (hydrophobic amino acids) to embed itself into the target membrane.
- The viral fusion protein inserts into the host cell’s plasma membrane > pulls 2 membranes together
what does fusion create? Why is this important?
- Fusion allows the creation of a fusion pore that allows viral nucleocapsids to be released into the cytoplasm
what property of the fusion protein is an important virulence factor?
- Changes in the fusion protein that influence its cleavage is an important virulence factor (ability of the virus to cause disease)- e.g., influenza virus and new castle disease virus
Which of the following statements is CORRECT about virus entry into the cell?
a. Virus tropism is shaped by availability of cellular receptors for virus entry
b. Direct penetration can be used by some viruses to enter into the cell
c. Virus-cell fusion is commonly used by enveloped viruses
d. Cleavability of the fusion protein is an important virulence factor
e. All of the above
e. All of the above
what occurs in the uncoating stage of viral entry to a cell? Where does this occur for RNA and DNA viruses?
ØThe virus particle is metastable: stable enough to move from cell to cell but primed to undergo structural changes and disassemble.
ØUncoating occurs when viral genome and capsid proteins separate
ØNucleocapsid proteins are enzymatically digested or destabilized to release the nucleic acid/genome
ØRNA viruses uncoat in the cytoplasm with few exceptions ØDNA viruses uncoat in the nucleus with few exceptions
what does viral genome replication involve?
Genome replication involves transcription, translation of proteins and replication of the genome to produce progeny virus
where does a DNA virus replicate and what does it require?
DNA virus: replicates using the host cell DNA polymerase, and it is transcribed by the host cell RNA polymerase
-in the nucleus with few exceptions
where does an RNA virus replicate and what does it require to do so?
- RNA virus: host cell does not have a mechanism to replicate the genomic RNA. Viruses encode RNA dependent RNA polymerase to replicate their RNA genome.
-in the cytoplasm with few exceptions
what do viruses need to synthesize their proteins?
Viruses need cellular ribosomes to synthesize their proteins. Cellular ribosomes only read mRNA!
how do + and - sense RNA viruses differ in their requirements for protein synthesis?
Positive RNA viruses: their genome is ready to be processed by ribosomes, so it acts as its own mRNA
Negative RNA viruses: their genome is not readable by the ribosomes, so it must be first converted to positive sense RNA by RNA dependent RNA polymerase (RdRp) prior to translation. Negative sense RNA viruses must package RdRp within their virion so it can readily start replicating the genome.