Module 10 - Viral Replication Strategies Flashcards
In order to replicate, what must all viruses do?
- Recognize host cells
- Make genome available to host cell machinery
- Replicate genome
- Make multiple copies of required proteins
- Assemble new viral particles
- Exit the cell
What is the consequence of viruses having a narrow host range?
They can only infect and replicate within specific cells
What determines the host range of a virus?
The interactions between viral and cellular proteins
What does the viral attachment protein do?
Interacts with the receptor on the host cell to allow entry
How come receptors cannot be eliminated to prevent infections?
These receptors are generally essential for the host cell
What is the cellular function of the CD4 receptor?
Immune cell interactions
What virus attaches to the CD4 receptor?
HIV (Retroviridae)
What is the cellular function of the ICAM-1 receptor?
Cell adhesion
Which virus attaches to the ICAM-1 receptor?
Rhinovirus (Picornaviridae)
What is the cellular function of the Bgp 1a receptor?
Cell adhesion
Which virus attaches to the Bgp 1a receptor?
MHV-A59 (Coronaviridae)
What is the cellular function of the CR2 receptor?
B-cell activation
Which virus attaches to the CR2 receptor?
Epstein-Barr virus (Herpesviridae)
What is the cellular function of the sialic acid receptor?
Various functions
Which viruses attaches to the sialic acid receptor?
Influenza virus (Orthomyxoviridae)
What is the cellular function of the OmpF receptor?
Transmembrane channel
Which virus attaches to the OmpF receptor?
T2 (Myoviridae)
What receptor does HIV (Retroviridae) bind to?
CD4
What receptor does Rhinovirus (Picornaviridae) bind to?
ICAM-1
What receptor does MHV-A59 (Coronaviridae) bind to?
Bgp 1a
What receptor does Epstein-Barr virus (Herpesviridae) bind to?
CR2
What receptor does Influenze virus (Orthomyxoviridae) bind to?
Sialic acid
What receptor does T2 (Myoviridae) bind to?
OmpF
What are bacteriophages?
Viruses that infect bacteria
What do most bacteriophages uses for attachment?
Tail fibers which recognize receptors present on the surface of bacterial cells
What 2 molecules does T2 recognize?
Lipopolysaccharide, and the outer membrane protein porin F precursor (OmpF)
What bacteria does T2 infect?
K-12 strain of E. coli
What strain of E. coli can T2 not infect?
O157:H7 (pathogenic strain)
What proteins are found at the tips of the T2 phage?
GP37 and GP38
How was it proven that T2 host range was due to strain specific differences in receptors?
The proteins on T2 tail fibers were replaced with proteins from a phage that could infect O157:H7 E. coli
What happened when the proteins on T2 tail fibers were replaced with proteins from a phage that could infect O157:H7 E. coli?
The T2 phage could not infect K-12 E. coli, but it could infect O157:H7 E. coli
How do enveloped viruses attach to host cells?
By a specific viral protein embedded within the envelope
What viral attachment protein is found in H1N1 influenza virus?
HA
What does HA stand for?
Hemagglutinin
How does adenovirus attach to a host cell?
With a viral attachment protein that extends from the capsid
How does poliovirus attach to a host cell?
With a protein that is part of the capsid itself
What do adenovirus and poliovirus have in common?
They are both non-enveloped viruses
What virus have scientists used to study strain specificity?
MHV
What does MHV stand for?
Mouse hepatitis virus
What viruses are related to MHV?
SARS coronavirus and MERS coronavirus
How come two strains of mice showed different susceptibility to MHV?
They had different protein receptors
Compare the Bgp 1a and Bgp 1b receptor.
The two proteins are structurally similar, but differ in amino acid sequences
What is the consequence of the amino acid differences in the Bgp 1 receptor?
It changes the conformation, so MHV interacts more strongly with Bgp 1a than Bgp 1b
What must happen after a virus binds to a host cell?
The virus or its genome must enter the cell
After an enveloped virus binds to a host cell, what separates the viral genome from the cell?
Two lipid bilayers (the viral envelope and the plasma membrane)
What interaction triggers receptor mediated endocytosis of influenza?
HA with sialic acid glycoprotein
What method does influenza use to enter the host cell?
Receptor mediated endocytosis
What causes the conformational change of HA?
Acidification of the viral envelope
What happens when HA changes conformation?
It exposes a fusion peptide
What does the fusion peptide do in influenza virus?
It helps the fusion of the viral envelope and the endosomal membrane
What happens when the viral envelope fuses with the endosomal membrane?
The nucleocapsid is released into the cytoplasm
How does HIV anchor to a host cell?
The attachment protein gp120 binds to the CD4 receptor
What happens when gp120 binds to CD4?
There is a conformational change in gp120, allowing it to bind to the coreceptor
What happens when gp120 binds to the coreceptor?
This causes additional conformational changes, leading to the exposure of a fusion protein on gp41
What is the purpose of gp41 in HIV?
It has the fusion protein that helps the fusion between the viral envelope and the plasma membrane
What was the first antiretroviral drug approved by the FDA, and when?
Fuzeon in 2003
What does Fuzeon do?
It is designed to prevent entry of HIV by preventing fusion
How does Fuzeon work?
It binds to gp41, preventing conformational change and fusion
What does entry for non-enveloped viruses require?
Direct penetration of cellular membrane by virus particle or genome
Generally, how do non-enveloped viruses enter a cell?
Through receptor mediated endocytosis
How does receptor mediated endocytosis work?
Virus particles bind to the receptor on the cell surface, leading to endocytosis
What happens when a non-enveloped virus enters a cell through receptor mediated endocytosis?
The low pH of the endosome causes a conformational change in the capsid (similar to influenza HA protein)
What happens when the capsid undergoes a conformational change in the endosome?
It exposes a pore forming domain that leads to the formation of a hole in the membrane
What is the purpose of the pore forming domain in a non-enveloped virus?
It allows the viral capsid or genetic material to enter the cytoplasm of the host cell from the endosome
What type of virus is reovirus?
A non-enveloped virus
What part of a bacteriophage enters the host cell?
The genome (not the particle itself)
What happens when T4 binds to the receptor?
It leads to the contraction of the T4 tail
What is the result of the T4 tail contracion?
The tail core pushes through the cell wall, bringing the phage DNA in contact with the plasma membrane
How does the phage DNA in T4 enter the cell?
Through the help of a pilot protein
What does the pilot protein do?
It binds to the phage DNA, and helps it penetrate the plasma membrane
Where does the viral capsid go in a bacteriophage infection?
It remains outside the cell
True or false: plant viruses, like bacteriophages, inject their genome into host cells
False: they do not inject their genome
How do plant viruses enter cells?
They rely on the help of external forces, such as insects
How do insects help plant viruses?
- Insects feed on plants, damaging the cuticle and cell wall
- When feeding, insects may acquire viruses, and transmit the particles
How come plant viruses rely on external forces to enter cells?
Due to the tough cell wall
What is tomato yellow leaf virus?
A plant virus
For most mammalian viruses, what is needed to allow for the viral genome to interact with the required host cell machinery?
Some form of uncoating
What is the first step of poliovirus uncoating?
After binding, the particles undergo a conformational change, resulting in the loss of capsid protein VP4
What happens when poliovirus loses VP4?
VP1 can interact with the cell membrane
What does VP1 do?
It creates a pore through the cell membrane
How does the RNA in poliovirus get from the capsid to the cytoplasm?
It leaves the partially disassembled capsid through the VP1-induced channel
How many different replication groups are there?
7
How many DNA replication groups are there?
3 (dsDNA, ssDNA, dsDNA using RT)
How many RNA replication groups are there?
4 (dsRNA, + ssRNA, - ssRNA, ssRNA using RT)
What is Baltimore classification based on?
How the mRNA of different viruses is produced
What is a Class I virus?
dsDNA virus
How do Class I viruses make mRNA?
By using dsDNA genome as a template
Where does genome replication occur for Class I viruses?
Usually in the nucleus of host cells
What is an exception to the genome replication rule for Class I viruses?
Pox (replicates in cytoplasm using viral enzymes)
How do Class I viruses replicate the genome?
Through host cell DNA-dependent DNA polymerase
What is a Class II virus?
ssDNA virus
How do Class II viruses make mRNA?
By using a dsDNA intermediate
When does genome replication of Class II viruses occur?
As ssDNA gets converted into dsDNA, which serves as the template for more genomes
What is a Class III virus?
dsRNA virus
How do Class III viruses make mRNA?
From one strand (negative strand) of the ds genome
Where does genome replication of Class III viruses occur?
In the cytoplasm
How do Class III viruses replicate the genome?
Through viral RNA-dependent RNA polymerase
What is a Class IV virus?
ssRNA, positive sense