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A&D 2010: Viruses
Viruses (all lectures)
66
Medical
Professional
01/27/2007

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Term
HIV-1 genome
Definition
(+)ssRNA, diploid
Term
HSV-1 genome
Definition
dsDNA, linear
Term
Influenza A genome
Definition
(-)ssRNA, segmented
Term
Does usual viral taxonomy represent viral phylogeny?
Definition
No (ie, viruses are usually classified according to size, structure, genome type, etc., and not according to function or evolution)
Term
What percentage of the human genome was derived from viral elements?
Definition
45%
Term
What are the stages of the early viral growth cycle?
Definition
1. Attachment
2. Penetration
3. Uncoating
4. Replication
Term
During what phase of the viral growth cycle are viral genes expressed?
Definition
Both early and late phases
Term
How is attachment mediated in HSV-1, HIV-1, and influenza A?
Definition
Virus Viral protein Host receptor Host coreceptor
HSV-1 Envelope proteins Heparan sulfate Immunoglobulins
HIV-1 gp120, gp41 CD4 CCR5 (chemokine receptor)
Influenza A Hemagglutinin Sialic acid -
Term
Of HSV-1, HIV-1, and influenza A, which viruses affect most cells of the body?
Definition
HSV-1 and influenza A (HIV-1 is mainly limited to CD4+ T cells)
Term
How does influenza A enter the host cytoplasm?
Definition
Endocytosis; low pH in endosome triggers the synthesis of a fusion protein, which causes fusion. Involves a conformational change in hemagglutinin.
Term
What are the two general ways that HIV-1 can enter the cytoplasm?
Definition
Either like influenza A (via endosome) or by direct fusion with the plasma membrane
Term
Mechanism by which HIV-1 envelope fuses with host plasma membrane
Definition
1. gp120-CD4 interaction
2. gp120's fusion peptides are exposed
3. Interaction with CCR5 coreceptor
4. 6-helix bundle formed
Term
Mechanism of action of Fuzeon (aka T-20)
Definition
Inhibits the fusion of the HIV-1 envelope with the host plasma membrane
Term
Purpose of M2 protein on influenza A
Definition
Allows for acidification of virus after it has been endocytosed; acidification allows for uncoating
Term
Mechanism of action of amantadine
Definition
Inhibits M2 protein of influenza A, preventing viral acidification and preventing uncoating
Term
HIV-1 protein that stays behind at the plasma membrane following uncoating
Definition
Env
Term
HSV-1 component that remains on plasma membrane following viral uncoating
Definition
Envelope
Term
HSV-1 tegument protein that enters host nucleus and activates RNA pol II
Definition
VP16
Term
Are viral genes expressed before or after viral replication?
Definition
Both before and after!
Term
Where does transcription and replication occur within a cell infected with influenza A?
Definition
Inside the nucleus
Term
What protein transcribes (-)ssRNA to mRNA in influenza A?
Definition
Viral polymerase (which hijacks 5' caps from host mRNAs as primers)
Term
Of the viruses HSV-1, HIV-1, and influenza A, which can be treated with inhibitors of DNA synthesis?
Definition
HSV-1 and HIV-1, because influenza A infections don't involve DNA synthesis
Term
How can DNA synthesis be pharmaceutically inhibited in HIV-1 and HSV-1 infections?
Definition
AZT for HIV-1 and acyclovir in HSV-1
Term
The effects of AZT and acyclovir are limited to what cell types in HIV-1 and HSV-1 infections, respectively?
Definition
* AZT is toxic to all cells, regardless of whether they are infected
* Acyclovir is specific for HSV-1-infected cells because it requires activation by a viral thymidine kinase
Term
Initial treatments for HIV-1 mainly targeted what?
Definition
Reverse transcriptase (agents included zidovudine [AZT] and didanosine [ddI])
Term
HIV-1, HSV-1, and influenza A proteins that target the host plasma membrane
Definition
HIV-1
* gp120
* gp41

HSV-1 * Glycoproteins

Influenza A
* HA
* NA
* M2
Term
How do HIV-1's gag and pol attach to the host plasma membrane during assembly of the virion?
Definition
Via fatty acids (lipid anchors)
Term
How does influenza A's M1 protein attach to the plasma membrane during viral assembly?
Definition
Via M1's hydrophobic sequences
Term
Characteristics of the maturation process in HIV-1 development
Definition
Maturation is the cleavage of precursor polyproteins (eg, gag-pol) into viral enzyes; occurs just before or during release of virions
Term
General class of drugs that prevents HIV-1 maturation
Definition
HIV-1 protease inhibitors (eg, Ro 31-8959)
Term
Typical components of highly active antiretroviral therapy (HAART)
Definition
Two reverse transcriptase inhibitors and one protease inhibitor
Term
How does HSV-1 DNA incorporate into viral capsid?
Definition
Specific DNA-nucleocapsid binding inside host nucleus
Term
How does influenza's A genome associate with the capsid?
Definition
M1 protein translocates to host nucleus where it binds specifically to viral RNA
Term
How does the HIV-1 genome incorporate into the viral capsid?
Definition
The 5' Ψ (psi) integration signal, a secondary structure on HIV-1's genomic RNA, binds specifically to gag
Term
How does the host cell remain alive when HSV-1, HIV-1, and influenza A virus particles exit en masse?
Definition
Viral particles bud outward by a process similar to exocytosis, allowing the host cell to seal small nicks in the membrane following each particle's exit
Term
From which cellular structures do HSV-1, HIV-1, and influenza A gain their envelope?
Definition
* HSV-1: nucleus
* HIV-1: plasma membrane
* Influenza A: plasma membrane
Term
How do HIV-1 and influenza A viruses attempt to prevent reinfecting the cell from which they have budded?
Definition
* HIV-1 downregulates CD4 expression
* Influenza A's neuraminidase cleaves sialic acid
Term
Two neuraminidase inhibitors
Definition
* Zanamivir
* Oseltamivir (Tamiflu)
Term
How is release usually regulated for many viruses?
Definition
Temporally and spatially
Term
How can HIV-1 infect cells that don't express CD4?
Definition
* Use alternative receptor
* Transcytosis (analogous to how influenza A infects cells) across epithelium can deliver HIV-1 to bloodstream * Injury to barrier
Term
Following entry into CD4- cells, what cell types are most commonly infected by HIV-1?
Definition
* Macrophages
* Lymphocytes

(Because they're close by)
Term
Dendritic cells are thought to play a role in the early dissemination of what virus?
Definition
HIV-1
Term
Is DC SIGN, a receptor found on Langerhans cells, a receptor for HIV-1?
Definition
No, it's a trans-receptor capable only of carrying HIV-1. It doesn't allow HIV-1 to infect the Langerhans cell.
Term
What dendritic cell protein allows dendritic cells to disseminate HIV-1 particles to T cells?
Definition
DC SIGN
Term
Which is more capable of infecting epithelial cells, HIV-1 or HSV-1?
Definition
HSV-1, by far (HIV-1 is generally not able to infect epithelium)
Term
After infecting epithelial cells, does HSV-1 infect nearby or distant cells?
Definition
Typically nearby sensory neurons; distant infections occur so rarely as to be clinically insignificant
Term
What RNAs are required for HSV-1 to establish a latent infection?
Definition
LAT RNAs
Term
In what cell types does HSV-1 replicate prior to establishing a latent infection?
Definition
* Satellite cells
* Neurons
Term
How does HSV-1 travel between neurons?
Definition
By synaptic transmission
Term
Transmission of HSV-1 to the CNS is a risk factor for what disorder?
Definition
Encephalitis
Term
Typical location of influenza A infections
Definition
Epithelia of upper respiratory tract
Term
From which side of the cell (apical or basolateral) are HSV-1, HIV-1, and influenza A released?
Definition
* HSV-1: basolateral
* HIV-1: basolateral
* Influenza A: apical
Term
Proteolytic cleavage of which influenza A protein allows for ready transmission to neighboring epithelial cells?
Definition
Hemagglutinin (HA)
Term
Is viremia a prominent feature during the ongoing replication phase of an HIV-1 infection?
Definition
No; during this time, T cells are able to keep the viral load down so that viremia is not prominent.
Term
Four mechanisms of immunodeficiency in HIV-1 infection
Definition
* Direct (eg, massive budding)
* Apoptosis (viral protein-triggered)
* Innocent bystander (infection of neighboring cells) * Anergy (viral-protein-triggered)
Term
In what organ system are CD4+ T cells most affected?
Definition
Gastrointestinal system (because it hosts more than 50% of body's T cell population)
Term
How can HIV-1 promote neoplasia?
Definition
One way is for HIV-1's genome to be integrated adjacent to a cellular oncogene
Term
Define viral incubation period
Definition
Time before signs and symptoms of disease become obvious
Term
Do influenza and retroviruses cause acute or persistent infections?
Definition
* Influenza: acute
* Retroviruses: persistent
Term
Trivia about the Spanish flu
Definition
* 1918-1919
* Killed 20-40 million globally
* Also called La Grippe
* H1N1
* Primarily killed healthy young adults
Term
Are hemagglutinin and neuraminidase encoded on the same or different segments of RNA in the influenza A genome?
Definition
Each is coded by its own segment
Term
Reassortment of different hemagglutinin and neuraminidase isotypes is an example of antigenic shift or antigenic drift?
Definition
Antigenic shift
Term
Point mutations in hemagglutinin or neuraminidase of influenza A are examples of antigenic shift or antigenic drift?
Definition
Antigenic drift
Term
How often does influenza A exhibit antigenic drift and shift?
Definition
* Antigenic drift: every several years
* Antigenic shift: 10-20 years
Term
Persistent viral infections are usually mediated by viruses with what types of genomes?
Definition
Genomes that exist as DNA during the viral replication cycle (eg, herpes and HIV-1, but not influenza A)
Term
Define zoonoses
Definition
Diseases that can be transmitted between humans and other vertebrates
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