Exam 3 - Lecture 8

Question 1

Do a quick review of DNA viruses genome types and their replication (slide 1 here)

Answer 1

genome:
- ssDNA or dsDNA
- can be linear/circular, one piece/segmented

replication: most replicate their genome in the nucleus of the host cell

Question 2

Poxviruses
- What is unique about their capsid shape and genomic structure?

Answer 2

Brick shaped nucleocapsid

Linear dsDNA genome, with the two strands covalently bonded at each end to create hairpins

Question 3

Poxviruses
- Know the other unique characteristics of its structure

Answer 3

• multiple envelopes
• surface viral tubules rather than normal glycoproteins
• multiple layers of matrix, some without a specific function
• a large number of replicative enzymes

Question 4

Poxviruses
- Where does it replicate and why is that unique?

Answer 4

Poxviruses replicate in the cytosol rather than most DNA viruses which replicate in the nucleus in order to use the host cell’s machinery. Poxviruses must bring with them their own machinery to do this

Question 5

Poxviruses
- What enzymes must it package into virions because it replicates there?

Answer 5

poxvirus must bring its own RNA polymerase, transcription factors, mRNA capping enzymes and mRNA polymerase

Question 6

What two poxviruses can infect and cause significant disease in humans?

Answer 6

smallpox and monkeypox

Question 7

What is variola?

Answer 7

The poxvirus that actually causes smallpox

Question 8

How is smallpox spread, what cells does it infect, and what tissue does it target?

Answer 8

Spread through respiratory secretions, direct contact, and even indirect contact

Smallpox infects local immune cells, and then gets moved to the lymph nodes

Question 9

What disease symptoms does smallpox produce?

Answer 9

Characteristic pustule rash, fever, muscle ache, and fatigue

This can progress into hemorrhage, shock, and death

Question 10

What is vaccinia virus and how do we use it as a vector?

Answer 10

Vaccina virus a derivative of cowpox, and it’s used as our smallpox vaccines

Question 11

Herpesviruses
- What is the tegument?
- What gives them the ability to infect multiple tissues?

Answer 11

tegument: a diverse matrix layer inside the herpesvirus

they contain many glycoproteins which enable them to infect a variety of tissues

Question 12

Herpesviruses
- What is different about alpha, beta, and gammaherpesviruses?

Answer 12

The difference between these viruses is the type of cell that is secondarily infected by a herpesvirus:
- alpha: a neuron
- beta: leukocyte
- gamma: B/T cell

Question 13

Herpesviruses
- What generally meant by latency?

Answer 13

After primary infection, some capsids take the genome and bring it into another cell, and inside that new cell the virus goes dormant, and will stay their for the remainder of the infected individual’s lifetime

Question 14

Herpesviruses
- What are LATs and how do the mechanistically create a state of latency?

Answer 14

LATs (latency associated transcripts) are RNAs that shut down viral replication so that the herpes genome remains inactive

Question 15

Herpesviruses
- What triggers reactivation and what determines the frequency of reactivations?

Answer 15

Reactivation usually occurs following a period of stress to the individual

Frequency of reactivation is directly proportional to the inoculum level of the initial infection

Question 16

Know how herpesviruses express their genes. What types of genes are expressed as IE, E, and L?

Answer 16

Herpesviruses express their genes in waves, and there are typically three classes of genes:
- Immediate-early (IE) : right after entry, set up infection
- Early (E) - DNA replication, modulate cell metabolism
- Late (L) - structural proteins to be packaged into virions

Question 17

What are some ways in which herpesviruses evade the immune response?

Answer 17

1) Disrupt cellular MHC expression
2) Make fake (homologs) cytokines and receptors
3) Prevent NK cell recognition

Question 18

Know alphaherpesviruses and the diseases they cause (and who typically gets the diseases, etc.)

Answer 18

Herpes simplex virus (type 1 or 2, aka HHV-1 and HHV-2) and Varicella zoster virus (VZV, aka HHV-3)

Anyone can get HHV-1 and -2, spreads through any contact of mucous membranes
- Cause painful watery blisters on the mouth (1) or genitals (2)

HHV-3 causes chickenpox and later shingles

Question 19

Know betaherpesviruses and the diseases they cause (and who typically gets the diseases, etc.)

Answer 19

Human cytomegalovirus (HCM, aka HHV-5)

Nearly ubiquitous in the population (immunocompromised are at special risk), and infects every tissue in the body

Usually asymptomatic

Question 20

Know gammaherpesviruses and the diseases they cause (and who typically gets the diseases, etc.)

Answer 20

Epstein-Barr virus (EBV, aka HHV-4)
- Ubiquitous
- Infects epithelial cells and spreads to B cells
- Can cause mono, many forms of lymphoma, gastric cancer, and more

Kaposi-sarcoma herpesvirus (KSHV, aka HHV-8)
- causes SK, a skin cancer seen in HIV/AIDS patients
- most people harbor it asymptomatically, but immunosuppression allows for replication

Question 21

Papillomaviruses (PV)
- What tissue type does it target?

Answer 21

epithelial tissue

Question 22

Papillomaviruses (PV)
- What is a common property to all papillomaviruses in terms of tissue growth?

Answer 22

All >200 human papillomaviruses (HPV) cause excessive tissue growth
- Most present as benign warts, but some types cause cancerous lesions

Question 23

Papillomaviruses
- How do we prevent PV infections?

Answer 23

Infection of the most prominent cancer-causing types of HPV can be prevented with the vaccine Gardasil

Question 24

Papillomaviruses
- What do PV capsids look like and what is bound to the genome (and why)?

Answer 24

Icosahedral capsids

histones are bound to the genome to keep the genome organized like cellular chromatin

Question 25

Know how PV replicate through a 3-D tissue. What is unique about how it works? How does the virus gain access to the tissue and what cell type does it initially infect? How do virions get released?

Answer 25

HPV must gain entry into the basal layer of the skin through a wound to infect an individual
- usually on hands or feet because these are high-touch areas of the body

Infects skin cells, and viruses get sloughed off with dried squams, although the genomes stay in the basal layer unless destroyed