Old Exam 2 Questions Flashcards
(37 cards)
What is the route of entry into the host for a virus that is transmitted in the vector-human pattern?
Give an example, from the MB 461 case suited, of a specific, named virus that has this transmission pattern
break in the skin from a bite from the vector
Sindbis virus
What is the name given to the transmission pattern of a virus that causes zoonotic infection?
Give an example, from the MB 461 case study of
animal to human
Influenza A virus subtype H5N1
What are three routes by which virus infection potentially can spread through a human host?
blood, lymph, nerves
When they infect a human host, which of these routes is/are used by (i) poliovirus and (ii) Sindbis virus
(i) blood and nerves
(ii) lymph and blood
Which one of these factors normally restricts influenza A virus to cells of the respiratory tract?
Influenza A virus is unable to get to the specific tissue
After attachment of Sindbis virus to host cells, by what mechanism does penetration occur?
clathrin-mediated endocytosis
What event triggers the uncoating of Sindbis virus particles?
acidification of the late endosome
Briefly outline the mechanism by which Sindbis virus particles are uncoated, and identify the differences between the two models that have been proposed for this process?
In the acidic environment of the late endosome, the spike is triggered by a conformational change in the virion which is transduced to underlying nucleocapsid. This causes the E1 subunit of the spike to go into the endosomal membrane. From here, the two membranes can fuse, or the spike can open a channel or aqueous pore through the endosome membrane. The latter is the most likely. In either case, the viral RNA passes into cell cytoplasm.
What of these models is most similar to the uncoating mechanism used by (i) influenza A virus, and (ii) minor-group rhinoviruses
(i) fusion of the two membranes
(ii) opening of the channel through injection
Sindbis virus RNA synthesis requires the viral P1234 polyprotein. Describe the sequence of proteolytic cleavage events required to process P1234, and indicate which RNA species can be synthesize by each of the enzyme complexes created during the process.
- sequence of cleavage events is first, between sP3 and nsP4, creating P123 and nsP4. Can synthesize genomic (49S) (-)ssRNA
- cleavage between nsP1 and nsP2, creating sP1, P23, and nsP4. can synthesize genomic (49S) (-)sRNA and (+)sRNA
- final cleavage between nsP2 and nsP3, creating nsP1, nsP2, nsP3, and nsP4. Can synthesize genomic (49S) (+)ssRNA and subgenomic (26S) (+)ssRNA
What protease carries out these cleavage events?
nsP2
What type of proteases carry out the site-specific cleavage of viral polyproteins that occurs in (i) P-spaces, and (ii) E-spaces? (2 points). Name one specific protease of each type that is required during the infection cycle of Sindbis virus. (2 points).
P spaces= viral encoded enzymes - protease C
E spaces= host encoded enzymes - signalase
What are two specific ways in which poliovirus reprograms (‘hijacks’) infected host cells? (2 points). Which stage of the cellular infection cycle is facilitated by each?
- gene expression -. Cap binding protein inactivated by viral proteases. Blinding the ribosomes to only translate the viral genome. Translation of most mRNAs is blocked off.
- genome replication - vesicles fusion to cis-Golgi inhibited. Back up a “lake” of vesicles to add the replicase complexes. Creates more membrane area for replication to occur.
Briefly describe the events that occur during translation of the poliovirus genome. Begin your description when the ribosome first interacts with the RNA, and conclude after the ribosome reaches the termination codon at the end of the single ORF.
- Ribosome binds to RLP and initiates translation at nearby AUG codon of single, large ORF
- P1-2A polyprotein in fragment translated
- Protease 2A co-translationally cleaves nascent polyprotein to release P1
- Translation of polyprotein continues until P2-3ABC fragment completed.
- Protease 3C co-translationally cleaves to release P2
- Translation to generate P3
- eventually will reach termination codon
To what family and genus do influenza B virus belong?
family - Orthomyxoviridae
genus - INFLUENZAVIRUS B
What is the maintenance cycle for influenza A viruses of subtype H5N1? (2 points). How can these viruses be acquired by humans?
- animal to animal
- these viruses can be transmitted from animals to humans
One of the influenza A virus envelope spikes has neuraminidase activity. What chemical reaction does neuraminidase catalyze? (2 points). Name one antiviral drug that inhibits influenza A virus neuraminidase.
- neurominidase cleaves sialic acid glycosidic bonds
- Tamiflu
During the late stages of the influenza A virus cellular infection cycle, newly-formed nucleocapsids must be trafficked out of the nucleus. Provide a detailed outline of this process. Be sure to identify each of the viral proteins involved and the role that it plays.
- newly synthesized M1 is imported into the nucleus and binds to the nucleocapsids to cover NLS
- newly synthesized NS2 binds to the M1 with the NES of the NS2 protein still exposed therefore it will be recognized and exported out of the nucleus.
- NS2 recycled because concentration is low in cytoplasm
- nucleocapsid still covered with M1 so cannot import into the nucleus
What type of proteases carry out the site-specific cleavage of viral polyproteins that occurs in (i) P-spaces, and (ii) E-spaces? (2 points). Which of these two protease types are employed by picornaviruses?
P spaces= viral encoded enzymes - protease 2A and 3C
E spaces= host encoded enzymes - none
By what route of transmission do influenza viruses spread from person-to-person?
respiratory-aerosol (droplet)
From what host species was influenza virus A/Hong Kong/483/97 (H5N1) isolated? (1 point). Is this strain associated with propagated epidemics in humans? (1 point).
- Humans
- no
Briefly describe the process of “cap stealing” as it applies to the initiation of mRNA transcription during influenza A virus gene expression.
- viral transcriptase binds to 5’ end of nascent RNA messages.
- endoribonuclease activity that will cleave close to 5’ cap of RNA and take off 10-15 nucleotides.
- transcriptase uses 3’ OH on the 5’ on last nucleotide to extend its own transcription.
- final message will have cap and a few nucleotides from the cap and then the viral encoded sequence.
What is the name of the mechanism used to express the second ORF of bicistronic RNA segments, 7 and 8, of influenza A virus?
differential splicing
What four viral proteins are found in the influenza A virus envelope? Indicate their major function(s), and the stage(s) of the cellular infection cycle, prior to assembly of new virions, at which each is required.
HA proteins - one of the spike (attachment), conformational change causes fusion in endosomal membrane (uncoating)
NA glycoproteins - cleaves sialic acid. keeps virus particles from sticking to each other and that virus not sticky to the host cell (prep for release)
M1 protein - dissociates to allow nucleocapsid to be exported into nucleus (uncoating), attaches to NP covered nucleocapsid and covers NLS on both (genome replication)
M2 protein - acts as ion channel in lipid bilayer. Only allows protons to pass through (uncoating)
