1
Q
Define virulence. List 4 factors it is related to/determined by.
A
- the capacity of a virus to cause disease
- related to virus strain, dose or inoculum of the virus, inoculation route, and host factors
2
Q
Viral infections are often __________. Symptomatic infection are preceded by an _______________. Symptoms are very often linked to the __________.
A
- asymptomatic
- incubation period
- immune response
3
Q
4 different patterns of virus infection in people
A
- acute (common)
- chronic
- Latent, relapsing
- transforming infection
4
Q
Define a transforming infection.
A
-where the virus immortalizes the cell, giving rise to cancer
5
Q
Characteristics of acute, in vivo infections
A
- acute, self-limited, virus cleared by immune response
- may be symptomatic, but MORE OFTEN asymptomatic
- rapid production of virus
- rapid resolution and clearing of infection
- well suited for rapid spread: by the time patient is symptomatic, virus has already spread to new host
- modify innate immune responses
6
Q
Do DNA or RNA viruses often cause acute infections?
A
-RNA
7
Q
Viruses that cause acute infections may modify ___________ and rarely so will modify _________.
A
- innate immune responses
- rarely adaptive immune response
8
Q
Viruses that cause acute infections often shutoff _________. Why?
A
- host cell protein synthesis
- to make as much virus as possible; cell becomes a virus production factory, making nothing but virus
9
Q
How do Poliovirus and influenza shutoff host cell protein synthesis yet keep theirs on?
A
- Polio: cleaves cellular EF4, preventing host mRNA translation. However, it have secondary structures in its RNA that support ribosome binding so that only viral proteins are produced
- Influenza: “steals” 5’ caps from cellular mRNAs so they cannot be translated. It then uses the caps for viral mRNA and again, only viral proteins are produced
10
Q
Viruses that cause acute infections shutoff host cell protein synthesis and are often _________. Explain.
A
- cytopathic
- they replicate quickly, killing the cell and producing new virions; cells experience morphological changes as result of infection
11
Q
Give 4 examples of cytopathic effects observed due to an acute infection.
A
- inclusions: sites within cells that are packed with viral proteins; “viral factories”
- syncytia: multigiant nucleated cells
- cell swelling
- cell death from apoptosis
12
Q
Some cytopathic viruses induce cell fusion (syncytia). Give 3 steps to describe how this happens.
A
- virus infects cell
- viral fusion protein delivered to surface
- infected cell fuses with adjoining cell
surface proteins help virus fuse with cell, but also help infected cell fuse with uninfected cell
13
Q
What branch of the immune system do viruses causing acute infections have to deal with?
A
- innate immunity
- adaptive would protect you from subsequent infections, but not help with the initial; this is the job of the innate immunity
14
Q
_________ is the hallmark of the innate response to virus infection. Which type are particularly important.
A
- interferon release
- Type I interferons like IFN-alpha and beta
15
Q
Describe IFN production
A
- there is one IFN-B and many IFN-a genes
- induced by dsRNA, ssRNA, DNA in cytoplasm/endosome by TLRs
- induce positive feedback loop through upregulation of receptors and IFNa/b genes
- can be produced by almost all cell types
16
Q
Why is interferon release said to be “altruistic”?
A
-IFN is released by an infected cell, bind to its receptors on neighboring cells, and induce an anti-viral state in them as a form of protection
17
Q
List 3 examples of proteins induced by IFN to produce an anti-viral state and these proteins effects
A
- Protein kinase R (PKR): phosphorylates EF2a and inhibits translation
- Rnase L: degrades all mRNA in cell
- Mx protein: binds to some viral proteins and inhibits virus assempby: transcriptional inhibition and inhibition of virus assembly
18
Q
Viruses that cause acute infections usually inhibit ___________ or ____________ or _________via many mechanisms. The balance between host defense and viral offence determines virulence.
A
- IFN production or the response to IFN
- apoptosis
19
Q
Characteristics of chronic viral infections
A
- virus particles or products are made for prolonged periods of time, continuously or intermittently
- often but not always caused by DNA virus
- may be ultimately cleared, but some remain for lifetime
20
Q
For a virus to persist and be a chronic infection, it must shutdown what activities that it may encode?
A
- lethal/cytolytic; become noncytopathic
- **Virus lifestyle: live and let live, stay under the radar
21
Q
Viruses that cause chronic infections in vivo are usually non-cytopathic in vitro. Explain.
A
-actively produce new virions without killing the cell
22
Q
Disease symptoms of chronic viral infections are often the result of what?
A
-the immune response that kills infected cells
23
Q
Viruses that cause chronic infections have to exist in the face of an evolving _________. They do so via what 3 mechanisms?
A
- adaptive immune response
1. viruses can mutate and evolve, staying ahead of the immune response
2. produce proteins that modify the immune response
3. establish a latent infection and wait for immune response to subside
24
Q
Give an example of how a virus can modify the host immune response as a way of establishing a chronic infection.
A
- encode proteins that down-regulate MHC class I proteins
- can block this along any step of MHC class I formation and surface production
25
Latent infections are largely a property of _______ viruses.
-herpes
26
Describe the protein production of a latently infected cell. What can reactivate these cells?
- cell either makes no virus proteins, or only a few that keep it in latent state
- no protein production= cell is not seen as being infected by immune system
- cells can be reactivated by stress, decrease in immune surveillance
27
Give 2 examples of latent infections
- HSV and cold sores
| - varicella zoster causing chicken pox in child and shingles in later life
28
What are common sources of virus?
- most human infections are caused by viruses that only infect humans, and so infected humans are often the course of the virus
- viruses can infect animals which can spread it
- viruses can be spread by insects that spread it from animals to humans as well
29
List 4 different routes of transmission. Which is the most common?
1. skin/mucous membrane
2. urogenital tract
3. Alimentary tract
4. respirtatory tract** most common route of viral entry
30
2 ways viruses are spread via respiratory tract as a route of transmission
1. aerosolized droplets frequently contain viruses: rhinoviruses, influenza, coronaviruses, adenoviruses
2. infection can also spread via infected saliva
31
Defense mechanisms to respiratory tract routes of virus transmission
- mucociliary action: viruses trapped in mucus, carried to back of throat and swallowed
- alveolar macrophages ingest foreign material in alveoli
- neutralization by IgA
32
Specialization and the respiratory tract
-viruses evolve to infect particular regions of the respiratory tract, giving rise to different clinical presentations
33
What are the defense mechanisms to alimentary tract as a route of viral infection? List 4 viruses that infect it. Which type of viruses typically don't survive this route?
- acid pH, proteases, bile detergents, dilution, cilia, and mucus
- Polio (fecal-oral route), reoviruses, rotaviruses, Norwal calcivirus
- enveloped viruses typically dont survive this route
34
Defense mechanisms to Urogenital tract (Sexually transmitted viruses) as route of transmission. What can increase transmission efficiency?
- mucus, low pH, squamous epithelium
| - pre-existing ulcers, lesions increase risk and transmission efficiency
35
Defense mechanisms to skin/mucus membrane as route of viral transmission. What is needed for these infections to occur?
- dry, keratinized cells form an effective barrier, epidermis lacks blood vessels/lymphatics to limit spread
- need breaks/abrasions in the skin (sometimes by an insect vector)
36
What is worrisome about a virus gaining entry to the dermis rather than the epidermis?
-dermis has blood supply and it may spread to other sites in the body
37
Viruses may be disseminated as individual virus particles, or they may be transmitted as _________.
-cell-associated virions
38
What is an emerging concept within viral dissemination?
-while viruses can't move on their own, they frequently usurp host pathways to get them to where they need to go between tissues, between cells, and within cells
39
Hematogenous spread definition and clearance
1. hematogenous spread: may enter bloodstream via capillaries, replication in endothelial cells, inoculation by vector bite
- cleared by neutralizing antibodies, cells of the reticuloendothelial system, binding and infection of new target cells
40
2 examples of passive viral dissemination
1. hematogenous spread
| 2. lymphatic spread
41
Viremia
-presence of infectious virus particles in the blood
42
T/F: viruses only disseminate via passive methods.
-false; they actively disseminated by hitching a ride on migratory cells
43
HIV and lymphatic dissemination
-HIV attaches to dendritic cells which transport HIV to the lymph nodes where it infects T cells
44
Why would viruses evolve the ability to move along the cell surface?
-viruses usually encounter surfaces of epithelial cells first. The surfaces are often an inhospitable place for a virus and so by surfing, the virus can move to the base of the cilia where it can be endocytosed and lead to infection
45
Aside from surfing, another way viruses can move is by what method?
- triggering signals that induce the cell to engulf the virus
- drugs that stop this also block infection
46
Pox virus and 2 active movement mechanisms of its infection
1. surfs along surface of filopodia
2. when reach cell surface, they transduce signals that causes the cell to then internalize the virus by a process called macropinocytosis
47
Active dissemination can occur in 3 ways; we have already discusses surfing outside cells/trafficking with them, triggering endocytosis, what is a third way?
-movement within a cell via microtubules
48
Retrograde vs. anterograde spread
- retro: movement of virus towards a cell body
- antero: movement of a virus away from cell body
* viral proteins can mediate movement along MTs
49
HSV 1 and 2 move along MTs to travel within axons. _________ proteins interact with _______ after virus entry.
- viral tegument proteins
| - dynein
50
Incoming viruses use ______ to move towards the cell body and newly produced viruses use _______ to go towards the periphery.
- dynein
| - kinesis
51
Describe shingles presentation and mechanism
- Herpes zoster mainly affects a single, unilateral dermatome of the skin when latent virus reactivates in a sensory ganglion
- characteristic eruption of vesicles in the involved dermatome
- anterograde transport mechanism
52
Give mechanism for how viruses can also move efficiently from cell to cell actively without leaving the cell
- filopods from infected cell makes contact with a target cell
- long lived interaction established by envelope proteins binding to R on target cell
- virus surfing to site of contact
- endocytosis of the protrusion by the target cell
53
5 forms of active dissemination of viruses
1. attach to cells and taxi ride elsewhere
2. surf down surface of cell
3. trigger endocytosis
4. MT transport
5. cell-to-cell transmission via filapods/actin rockets
54
How does HIV disseminate from cell to cell?
- buds at sites of cell to cell contact, resulting in efficient virus spread because antibodies and other humoral immune methods cannot reach the virus
- large number of virions are transferred from the synapse/contact point to the target cell
55
Virus shedding definition
- release of infectious virus from infected host
- usually a requirement for transmission
- can occur locally at primary site of infection or via many routes for viruses that are disseminated in the host widely
56
What are the 3 major ways in which viruses cause disease?
1. direct cytopathic effects: death of host cell by apoptosis or lysis
2. Virus-induced immunopathology (4 types): virus itself isnt killing the cells, the IS is
3. Viral oncogenesis: cellular transformation by a virus
57
4 types of virus-induced immunopathology
1. cell-mediated
2. antibody-mediated
3. autoimmunity
4. immunosuppression
58
Ebola virus is an example of _________. Explain.
- disease caused by direct cytopathic effects
- Ebola virus glycoprotein (GP) spike protein induced "rounding of cells" and loss of surface attachment proteins. When this happens in endothelial cells, hemorrhagic fever and death results
* * this disease is caused directly by virus itself and its products
59
Dengue hemorrhagic fever is an example of _________. Explain.
- disease caused by antibody-mediated immunity
- Dengue virus has 4 serotypes, and antibodies to 1 do not neutralize others
- usually causes acute, self-limited febrile illness, but infection with SECOND serotype greatly increases risk for DHF and shock syndrome
- Mechanism: antibody dependent enhancement
60
Guillan-Barre Syndrome is an example of _________.
- disease due to virus-initated autoimmunity
- ascending paralysis due to immune mediated destruction of host myelin thought to be due to immune targeting of myelin basic protein
61
HIV and measles are examples of ___________.
- diseases caused by virus-induced immunosuppression
- HIV infects and destroys CD4+ T h cells, leading to immunosuppression
- Measles: infects DC and monocytes and reduces antigen processing and presentation. This inhibits proliferation of lymphocytes and places patients at risk for other infections
62
Define cellular transformation and what does virus-induced tumorigenesis lead to?
- progression of genetic and cellular changes that lead to the development of cancer
- uncontrolled proliferation of cells that are clonal (originating form an initial parental cell)
63
Virus-induced tumors can be benign or malignant. What is a hallmark of malignancy?
-metastasis is hallmark of malignant tumors, but not all malignant tumors metastasize
64
About ______ of human cancers are viral in origin. Other these, about ______ are liver and cervical.
- 20%
| - 70%
65
5 major mechanisms of viral transformation
- targeting tumor suppressor like pRb and p53
- inappropriate expression of growth factors
- induction of chronic injury (Hep B)
- retroviruses can encode oncogenes
- viruses can also lead to tumors more indirectly by causing immunosuppression for prolonged periods of time
66
Define Oncogene, cellular-onc, and viral-onc
- oncogene: gene whose protein product functions as a major effector in conversion of normal cell to a cancerous cell
- Cellular-onc: cellular gene activated in tumor cells or a normal gene altered to become an active oncogene
- Viral-onc: viral homolog of a normal cellular gene or a viral gene with no homology to cellular genes which when activated functions as a tumor inducer
67
Structure of HPV
- small, non-enveloped DNA viruses that infect the skin and mucosal epithelia
- >140 types identified
68
HPV types that are closely associated with ____________ have been designated "high-risk" types. What are low risk types?
- human cancers (cervical cancer for 16, 18, 31,33)
| - benign growths like warts (6,11)
69
4 general categories of HPV-induced diseases
1. skin warts
2. genital or anal warts
3. respiratory papillomatosis
4. cancer
70
What is the most important risk factor for cervical cancer development?
- HPV infection
- its genome is found in over 95% of cervical cancers
- malignant cancer development requires a long period after initial HPV infection
71
T/F: not all women with HPV infection will develop cervical cancer.
-True
72
Papillomavirus tropism
- specifically infects squamous epithelial cells
| - infects cells within the dividing basal epithelial layer
73
Transformation mechanisms of high-risk HPVs
- HPV DNA is integrated into host genome
- integration specifically disrupts or deletes E2 gene which normally inhibits E6 and E7 protein production
- E6 and E7 functions as oncogenes that promote tumor growth and malignant transformation by inhibition tumor suppressor genes p53 and RB
74
A _________ HPV infection is required for malignant progession.
-persistant
75
Name the 2 HPV vaccines currently on the market
- Gardasil: blocks 16,18, 6, and 11 to prevent cervical cancer and warts
- Cervarix: only blocks 16 and 18 to prevent cervical cancer strains
- based on hollow-virus-like particles (VLPs) assembled from recombinant HPV coat proteins
76
Where were the HPV vaccine's results seen?
- in vaccine types only
| - not in rates of older women
