Virus Families, Replication and Drugs Flashcards
Describe the viral life cycle.
Herpes Virus
- What is the genome like?
- How many proteins do they encode?
- Are they enveloped or not?
- Where do they replicate?
- Describe the key characteristics of herpes infection.
- dsDNA
- 35
- Enveloped
- Nucleus - require our RNA polymerase to transcribe genes but have their own DNA polymerase genes to replicate genome
- It is a latent virus, meaning a person can carry it but not have an active outbreak. The virus can be reactivated by stressors and produce infection. This is a lifelond infection that does not go away, carriers will always have the virus in its latent form when not experencing active outbreak.
What are the 2 herpes viruses that alway result in an obvious initial infection?
Chicken Pox and (Varicella Zoster Virus)
Mononucleosis (Epstein-Barr Virus)
What are the 3 families of herpes viruses?
What viruses are in each family?
Alpha herpesviridae (HSV1, HSV2, VZV)
Beta herpesviridae (CMV, HHV6, HHV7)
Gamma herpesviridae (EBV, HHV8)
What happens upon binding of HSV to host cell?
HSV viral host shutoff protein (tegument protein) is released into the cytosplasm and initiates the degradation of host cell mRNA
In HSV, what are:
- Alpha trans-inducing factor
- Alpha genes
- Beta genes
- Gamma genes
- After entry to host cell, alpha TIF is transported to nucleus, viral capsid also migrates to nucleus where its DNA enters the nucleus and circularizes and alpha TIF induces the expression of alpha genes
- mRNA for the alpha genes are translated on ribosomes and protein products then enter nucleus and express viral beta genes
- Proteins from beta genes are involved in degrading cellular chromatin and localizing cellular DNA to inner side of nuclear envelope
- Gamma genes encode proteins that are structural for the virus
What does it mean to say that viral DNA is replicated as a concatamer?
Initial transcription/translation of alpha genes into proteins –> alpha proteins travel to nucleus and allow transcription/translation of beta genes from viral DNA –> beta proteins allow transcriptoin of gamma genes
Process repeats in a cycle.
Explain the process of herpes virus replication.
Virus binds to specific receptors on cell surface –> fuses with membrane –> shut off proteins begin to degrade host mRNA –> alpha TIF enters nucleus –> capsid travels to nucleus and viral genome enters nucleus –> alpha TIF induce expression of alpha genes (immediate genes) which take over cellular machinery –> alpha gene proteins induce transcription of beta genes (early genes) which include enzymes needed for viral replication and viral DNA polymerase –> beta genes induce transcription of gamma genes (late genes, structural, capsid and glycoprotein) –> Capsid proteins migrate into nucleus and assemble into mature capsids with genetic material –> traverses ER and Golgi before being released from cell
HSV infects _____ (cell type)
Neurons
HSV travels along the neuron in a _______ direction.
Retrograde
Where is the HSV genome kept once it enters a cell?
In an episome –> separate from host cell DNA
How does acyclovir function as an antiviral for HSV without impacting the host’s cells?
It mimics the structure of guanosine, but it lacks a 3’ OH group. When it is incorporated into growing DNA chains, it will interrupt the synthesis of a growing DNA chain. It is able to selectively target cells infected with the virus because acyclovir requires thymidine kinase to be active and cells that have been infected with HSV have much more active thymidine kinase compared to normal host cells. As such, acyclovir will only be activated in cells infected with HSV.
Acyclovir is a ______ inhibitor of viral DNA polymerase.
Competitive
Another name for influenza is ________
Orthomyxoviruses
How are influenza viruses named?
Based on the Hemagglutinin and Neuraminidase proteins that are present on their surface
Describe the structure of the influenza virus.
Coated by hemagglutinin and neuraminidase proteins on surface
Contains 8 segments of negative sense ssRNA inside as well as protein pores to release contents
Why are new influenza vaccines necessary each year?
Because the virus can undergo antigenic shift (different viruses from the same family can infect the same host simultaneously and mix together to create a new virus that contains elements of each virus and will not be recognized by host immunity conferred from vaccination) or antigenic drift (a virus infects a host and its genome becomes altered inside the host via point mutations)
How does influenza replicate?
What does influenza steal from its host in order to protect its mRNA?
It cleave the host’s 5’ Cap from host mRNA and uses it to extend its own mRNA
What are the classes of influenza antivirals?
Neuraminidase inhibitors: active against influenza A and B
Adamantanes: act on viral membrane protein M2 (ion channel) and block its activity, active against influenxa A but not B
Xofluza - active against influenza A and B, targets viral RNA polymerase
HIV is an enveloped virus of the ____ subfamily, which are ____viruses
lentivirus
retro
Describe the interior structure of HIV.
Two viral strands of RNA in the core of the virus
Outer protein coat with lipid envelope and embedded glycoproteins that interact with the host cell receptors and are responsible for binding to the target cell.
Describe the process of HIV replication.
- Virus binds to CD4 molecules and one of two coreceptors, virus fuses with cell
- Virus penetrates into cell empties contents
- HIV RNA is transcribed to cDNA by viral reverse transcriptase
- cDNA becomes integrated into host cell genome via action of integrase
- Viral particles assemble and bud out of membrane taking some cell membrane witht them
- viral DNA is permanent part of genome for entire life
How many types of HIV virus exist?
HIV-1 spread from _______ and HIV-2 is confined to ______
Where is HIV suspected to have originated?
2 with 11 known subtypes
Central Africa, West Africa
From simian virus that is closely related to HIV
Describe the course of HIV infection.
- During the acute phase (0 - 12 weeks), the HIV infection is wide spread and the virus is seeding inside lymphoid organs
- During the latent phase the individual is asymptomatic and the viral load lowers and stabilizes
- During the late phase, the person develops symptoms and there is a rise in the amount of viral mRNA and a subsequent decrease in the CD4 T-cell count. Death occurs due to depletion of adaptive immune function, which makes the individual more susceptible to opportunistic pathogens.
Discuss the tropism of HIV.
HIV is dual tropic - it can affect both macrophages and t cells because these both express CD4. There are different co-receptors on the T cell vs. macrophage that the virus recognizes assist with entry into the cell.
Why is it often necessary to take multiple HIV antivirals?
Because the different drugs target differnet mechanisms of viral replication which is necessary because the virus is able to rapidly mutate so multiple courses of treatment are needed simultaneously to keep viral loads low
What are the 6 classes of HIV antivirals?
Reverse Transcriptase Inhibitor (nucleosidase or non-nucleosidase)
Protease inhibitors
Fusion inhibitors
CCR5 (co-receptor) antagonist
Integrase strand transfer inhibitors
Describe the process of HCV replication.
The virus enters the cell via receptor mediated endocytosis, then releases its (+) sense RNA into the cytoplasm where ribosomes on the rough ER translate the RNA into proteins. These proteins associate with the ER membrane and function to produce (-) sense RNA which then serves as the template to make more (+) sense RNA. Other proteins that were transcribed from the (+) sense RNA function to process the RNA and proteins and package them into the capsid, which is released via the golgi attached to a lipoparticle (this is an enveloped virus)
