Virus Families, Replication and Drugs

Question 1

Describe the viral life cycle.

Answer 1

Question 2

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.

Answer 2

• 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.

Question 3

What are the 2 herpes viruses that alway result in an obvious initial infection?

Answer 3

Chicken Pox and (Varicella Zoster Virus)

Mononucleosis (Epstein-Barr Virus)

Question 4

What are the 3 families of herpes viruses?

What viruses are in each family?

Answer 4

Alpha herpesviridae (HSV1, HSV2, VZV)

Beta herpesviridae (CMV, HHV6, HHV7)

Gamma herpesviridae (EBV, HHV8)

Question 5

What happens upon binding of HSV to host cell?

Answer 5

HSV viral host shutoff protein (tegument protein) is released into the cytosplasm and initiates the degradation of host cell mRNA

Question 6

In HSV, what are:

• Alpha trans-inducing factor
• Alpha genes
• Beta genes
• Gamma genes

Answer 6

• 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

Question 7

What does it mean to say that viral DNA is replicated as a concatamer?

Answer 7

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.

Question 8

Explain the process of herpes virus replication.

Answer 8

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

Question 9

HSV infects _____ (cell type)

Answer 9

Neurons

Question 10

HSV travels along the neuron in a _______ direction.

Answer 10

Retrograde

Question 11

Where is the HSV genome kept once it enters a cell?

Answer 11

In an episome –> separate from host cell DNA

Question 12

How does acyclovir function as an antiviral for HSV without impacting the host’s cells?

Answer 12

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.

Question 13

Acyclovir is a ______ inhibitor of viral DNA polymerase.

Answer 13

Competitive

Question 14

Another name for influenza is ________

Answer 14

Orthomyxoviruses

Question 15

How are influenza viruses named?

Answer 15

Based on the Hemagglutinin and Neuraminidase proteins that are present on their surface

Question 16

Describe the structure of the influenza virus.

Answer 16

Coated by hemagglutinin and neuraminidase proteins on surface

Contains 8 segments of negative sense ssRNA inside as well as protein pores to release contents

Question 17

Why are new influenza vaccines necessary each year?

Answer 17

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)

Question 18

How does influenza replicate?

Answer 18

Question 19

What does influenza steal from its host in order to protect its mRNA?

Answer 19

It cleave the host’s 5’ Cap from host mRNA and uses it to extend its own mRNA

Question 20

What are the classes of influenza antivirals?

Answer 20

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

Question 21

HIV is an enveloped virus of the ____ subfamily, which are ____viruses

Answer 21

lentivirus

retro

Question 22

Describe the interior structure of HIV.

Answer 22

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.

Question 23

Describe the process of HIV replication.

Answer 23

• 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

Question 24

How many types of HIV virus exist?

HIV-1 spread from _______ and HIV-2 is confined to ______

Where is HIV suspected to have originated?

Answer 24

2 with 11 known subtypes

Central Africa, West Africa

From simian virus that is closely related to HIV

Question 25

Describe the course of HIV infection.

Answer 25

• 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.

Question 26

Discuss the tropism of HIV.

Answer 26

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.

Question 27

Why is it often necessary to take multiple HIV antivirals?

Answer 27

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

Question 28

What are the 6 classes of HIV antivirals?

Answer 28

Reverse Transcriptase Inhibitor (nucleosidase or non-nucleosidase)

Protease inhibitors

Fusion inhibitors

CCR5 (co-receptor) antagonist

Integrase strand transfer inhibitors

Question 29

Describe the process of HCV replication.

Answer 29

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)