Virus-Host Interactions and Pathogenesis

Question 1

What is viral pathogenesis?

Answer 1

process by which a viral infection leads to disease

Question 2

What 7 factors affect viral pathogenesis?

Answer 2

1. effects of viral infections on cells
2. entry into the host
3. course of the infection - primary replication, systemic spread, secondary replication
4. cell/tissue tropism
5. cell/tissue damage
6. host immune response
7. virus clearance or persistence

Question 3

What are virulent viruses? What 4 factors affect viral virulence?

Answer 3

measure of the ability of the virus to induce disease in a particular host

1. ability of the virus to grow and multiply in a particular host
2. ability of the virus to invade the host
3. ability to evade the host immune response
4. ability to cause damage in the target host

Question 4

What viral/host-related factors affect viral virulence?

Answer 4

• age
• gender
• immune status
• virus concentration

Question 5

What are permissive cells? Non-permissive cells?

Answer 5

PERMISSIVE: support viral replication
NON-PERMISSIVE: viral infection cannot be established

Question 6

What are the 3 mechanisms of viral-induced diseases in the affected host?

Answer 6

1. damaging/killing target cells
2. induction of immuno-pathology
3. cell transformation (tumors)

Question 7

What are the 5 steps of viral replication in host cells?

Answer 7

1. viral entry
2. local/general viral spread and viral replication in target organcs (tropism)
3. viral evasion of host immune/inflammatory responses
4. viral shedding from host
5. host cell damage

Question 8

What are the 5 steps of viral replication?

Answer 8

1. viral entry
2. local/general spread in the host and replication in target organs (tropism)
3. viral evasion of host immune-inflammatory responses
4. viral shedding
5. host cell damage

Question 9

What must viruses do to undergo all 5 steps of viral replication?

Answer 9

1. ENTRY: evade host’s natural protective and cleansing mechanisms
2. SPREAD/REPLICATION: evade hosts immediate defenses and barriers to spread; take over necesary host cell functions for its own replication
3. EVASION: evade host inflammatory, phagocytic, and immune defenses long enough to complete the transmission cycle
4. SHEDDING: exit host at a concentration needed to ensure infection in the next host
5. DAMAGE: pathogenicity

Question 10

What are the 4 types of viral infections?

Answer 10

1. PRODUCTIVE: virus introduces its genome into the cells, replicates, and produced new viral progeny
2. LATENT: viral genome is incorporated into the host cell genome and an infectious virus is not produced immediately, rather in times of stress
3. ABORTIVE: virus initiates infection and produces no progeny
4. PERSISTENT: long-term viral infection when the immune system fails to clear acute infection

Question 11

What is recrudescence?

Answer 11

new outbreak of viral infection after a period of abatement or inactivity

Question 12

What is viral load?

Answer 12

concentration of virus in body/tissue

Question 13

What characterizes recurrent viral infections?

Answer 13

infections occuring when several episodes of acute infection one after another due to the inability of the immune system to completely clear the infection
(AKA persistent)

Question 14

Types of infection:

Answer 14

Question 15

What are lytic infections? Immune complex diseases?

Answer 15

LYTIC INFECTIONS - destruction of cells by viral replication at rates greater than their replacement

IMMUNE COMPLEX DISEASE - antibodies cause immunopathologic conditions by combining with the virus and forming a complex that is deposited in glomeruli and organs, causing inflammation

Question 16

Virus shedding and clinical signs:

Answer 16

Question 17

What does the typical curve of acute viral infection look like?

Answer 17

Question 18

What are the 4 main patterns of viral infection?

Answer 18

1. acute infection followed by viral clearance
2. acute infection causing accidental tissue infection with permanent damage despite viral clearance
3. persistent infection: latent, slow, transforming
4. long incubations

Question 19

What is viral persistence? What are 5 causes?

Answer 19

inability of the immune system to clear an acute viral infection

1. immunodeficiency (HIV infection)
2. transplant
3. chemotherapy
4. genetics
5. congenital infection

Question 20

What are 4 possible outcomes of persistent viral infections?

Answer 20

1. no affect
2. chronic or progressive infections
3. cancer
4. clinical reactivation

Question 21

Why is viral persistence significant?

Answer 21

maintains a virus in the animal population

Question 22

As a viral infection persists, what must it overcome?

Answer 22

• after incubation, it must overcome the innate immune system to cause acute infection
• to progress to a persistent infection, the host must remain alive and it must overcome the adaptive immune system

Question 23

What are 6 mechanisms that allow for viral persistence?

Answer 23

1. viral evasion of the host immune response
2. modulation of adaptive immune system
3. induction of latency
4. infection of tissues not readily accessible to the immune system (keratinocytes)
5. immune response escape mutants
6. prolonged survival of infected cell (oncogene)

Question 24

What are 5 routes of entry for viral infection?

Answer 24

1. RESPIRATORY: inhalation of droplet nuclei of 1-10μm causes infection; 1-3μm penetrate bronchioles
2. SKIN: intact skin can be breached by insect bites, animal bites, and contaminated instruments
3. GENITAL TRACT: venereal infection rare
4. PLACENTA: viremia in pregnant female may cross the placenta and infect fetus
5. ALIMENTARY: virus ingested with food and water or licking of contaminated objects
6. CONJUNCTIVA

Question 25

What must viruses overcome in the respiratory and alimentary tracts to cause infection?

Answer 25

RESP: mucociliary clearance (ciliated epithelium), phagocytosis by alveolar macrophages in the lung, mucus secretion, lower temperature ALIMENTARY: low pH of stomach, high pH of intestine, mucous layer, peristalsis

Question 26

What are the 5 possibilities of the aftermath of a killed fetus via placenta transmission?

Answer 26

1. infertility 2. mummified fetus 3. abortion 4. stillbirth 5. surviving fetus with congenital abnormalities

Question 27

How does Rhinovirus infection affect the trachea?

Answer 27

kills ciliated epithelium, causing it to slough off - no longer looks like a carpet

Question 28

What is the pathogenesis of Ectromelia (Mouse-pox) virus?

Answer 28

1. skin invasion 2. multiplication in regional lymph nodes 3. primary viremia and multiplication in spleen and liver 4. secondary viremia and skin multiplication 5. primary infection - foot swelling - early rash = papules - severe rash = ulceration

Question 29

What are the major 3 ways that virsues are transmitted by the respiratory system?

Answer 29

1. DROPLET: transmitted from one individual to another by droplets of moisture expelled from the upper respiratory tract through sneezing/coughing 2 AEROSOL: transmitted by infectious particles or droplets through inhalation or direct contact with mucous membranes in the respiratory tract or eyes 3. FOMITE: clinical contact surfaces such as dental units, X-ray machines, equipment knobs, or housekeeping surfaces

Question 30

Where does primary and secondary viremia occur? What are some common sites in the body for viral replication?

Answer 30

PRIMARY: in the blood after the virus has passed through the host's natural barriers, like skin or mucous membranes SECONDARY: in the blood after the virus has reached primarily replicated in muscle, liver, spleen, or blood vessels - skin, mucous membranes, lung, kidney, GI tract, brain

Question 31

What do viruses that infect via skin penetration require? What are the 4 major methods of entry?

Answer 31

the ability to breach in the physical integrity of the effective barrier - cuts, abrasion, keratin damage 1. trauma of milking or suckling 2. arthropod bites 3. infected needles 4. animal bites

Question 32

What is shingles? What is its pathogenesis?

Answer 32

viral disease caused by chicken poxvirus characterized by painful skin rash with blisters in a localized area - infection breaches conjunctiva and upper respiratory tract - replication in the primary lymph nodes - primary viremia - replication in liver, spleen, and other organs - secondary viremia - infection of the skin and appearance of skin rashes - infection of sensory ganglia and establishment of latent infection

Question 33

What is the incubation period? What affects its duration?

Answer 33

time between the entrance of the virus into the body of the infected host and the appearance of clinical signs 1. respiratory virus (influenza) = few days 2. maedi-virus, rabies = several weeks/months

Question 34

What are the general steps of systemic infection?

Answer 34

1. virus multiplies at the site of entry and in the lymph nodes, resulting in primary viremia 2. virus reaches the target organs through secondary viremia and multiplies, resulting in cell damage and disease development - virus reaches skin via bloodstream to produce skin rashes - virus spreads to brain via cerebellar blood vessels or peripheral nerves - transplacental transmission may occur in pregnant animals

Question 35

How does the route of entry affect viral shedding?

Answer 35

- local spread from route of entry restricts viral shedding to respiratory secretions - viremic spread from the route of entry results in shedding from multiple mucosal surfaces

Question 36

What must viruses that cause systemic infection and spread via blood be able to do?

Answer 36

infect, replicate, and survive in lymphocytes and macrophages

Question 37

How do viruses invade the epithelium and spread via the lymphatic system?

Answer 37

- amplifies in the epithelium or infect sub-epithelial macrophages - cell-free virus or infected macrophages/DC pass to regional lymph node via afferent lymphatics - viral progeny released into venous secretions to cause viremia that can be cell-free or cell-associated

Question 38

How does rabies able to be transmitted? How does the location of transmission affect infection?

Answer 38

- rabies infected wild animal bites - inoculated virus moves in nerve tissue (retrograde) - virus reaches the brain and replicates - virus reaches salivary gland of affected animals - closer bite to brain = shorter incubation period

Question 39

What are the 2 possible ways that rabies and pseudorabies is able cross synaptic junctions?

Answer 39

1. retrograde infection: spread of virus from the axon terminals to the neuronal cell body and is directionally opposite to movement of the nerve impulse 2. anterograde infection: spread from neuron cell body toward axon terminus

Question 40

What is the purpose of virus shedding? How does this typically occur?

Answer 40

maintains the circulation of the virus in certain animal populations same route of entry - SKIN: direct contact with abrasions and wounds - RESPIRATORY: coughing and sneezing (large droplets = fall on objects; small droplets = airborne) - ALIMENTARY: feces (must be environmentally resistant) - GENITAL: semen, genital secretions during coitus or artificial conditions - KIDNEY: urine - BLOOD: arthropod bites, contaminated needles, tissues from animals in slaughterhouses - MAMMARY: milk

Question 41

What is viral tropism? What 6 things affect tropism?

Answer 41

affinity of certain viruses to certain tissues 1. cell receptors for the virus 2. cell transcription factors that recognize the viral promoters and enhancer sequences 3. ability of the cell to support viral replication 4. physical barriers 5. local temperature, pH, oxygen levels, tension 6. digestive enzymes, bile, etc. that inactivate viruses

Question 42

What is the mechanism of viral tropism? What are post-entry factors?

Answer 42

cellular receptors differentially expressed in certain cells limits viral entry into specific cell types factors within the cell that make them permissive to vral cells after entry (transcription and translational machinery, innate antiviral defenses overcame by viral-encoded proteins)

Question 43

What tropism does nervous tissue, digestive system, skin, respiratory system, and various body organs/tissues have?

Answer 43

NEUROTROPIC - rabies, EEV, WNV, NDV VISCEROTROPIC - rotavirus, BCoV, NDV DERMOTROPIC - poxvirus, LSDV, papillomavirus PNEUMOTROPIC - SARS-CoV, MERS-CoV, IBV, ILTV PANTROPIC - SARS-CoV2, IBV, RPV

Question 44

What determines influenza virus tropism?

Answer 44

availability of host proteases to cleave inactive viral proteins into active ones

Question 45

What are 5 viral determinants of survival and transmission?

Answer 45

1. viral envelope - surface protein expression and modification for the sit of infection, host receptor specificity and affinity, and formation of viral aggregates 2. viral capsid - structure and stability 3. internal proteins - polymerase for host-adapted replication 4. viral genome - densely packaged for stability 5. mutation - protects from host adaptation

Question 46

What are the 4 major outcomes of infection at the molecular and cellular levels?

Answer 46

1. cell death (cytopathic/cytocidal) - necrosis/apoptosis with the production of daughter viral particles*** 2. persistent infection - no apparent change, constant production of virus without cell destruction 3. transformation (hyperplasia) - alters cell morphology, but daughter virus may not be produced (tumors) 4. abortive infection - cell may be damaged, killed, or transformed, but no daughter virus is made

Question 47

What do cytocidal viruses do? In what 5 ways do they do this?

Answer 47

ceases the cellular macromolecular synthesis of important proteins, leading to rapid destruction of the infected cells 1. shut down cellular RNA and protein synthesis 2. accumulates viral macromolecules during replication 3. toxic capsid proteins 4. accumulate ciral components at the site of multiplication forming inclusion bodies that can distort cells and increase permeability 5. cause cellular lysosomal enzymes to leak out, resulting in autolytic digestion

Question 48

What do direct damage of the cells, edema, and immune system damage result in?

Answer 48

impairment of affected organ inflammatory exudation and infiltration immunodeficiency or immunosuppression

Question 49

In what 3 ways can antibodies cause cellular damage?

Answer 49

induce the formation of immune complexes (ab-ag) that can enhance infection, damage kidneys and joints, and cause persistent inflammation

Question 50

Cytopathic effects:

Answer 50

pathological effects of virus on infected cells

Question 51

What are the main 3 cytocidal viral effects

Answer 51

1. CPE 2. syncytia 3. inclusion body formation

Question 52

What is syncytia? What causes it?

Answer 52

cell fusion - multinucleated giant cells enveloped viruses with fusion proteins infect cells and cause new fusion proteins to be translated, which are transported to the cell surface and expressed on the membrane, allowing budding viruses to pick up the proteins and the fusion of the infected cells to neighboring uninfected cells

Question 53

Where are inclusion bodies found?

Answer 53

at the site of replication either in the nucleus (most DNA viruses) or cytoplasm (most RNA viruses) - can be large or small, eosinophilic or basophilic

Question 54

How are cytocidal viruses able to shut down cellular macromolecular synthesis?

Answer 54

code for early proteins that stop the synthesis of cellular RNA proteins

Question 55

How does the cytocidal virus' release of enzymes by lysosomes cause cell damage?

Answer 55

increases permeability of the cell's membrane allowing the movement of important components out of the cell

Question 56

How can cytopathic viruses affect the membrane of an infected cell? Cell chromosomes?

Answer 56

- express their peplomers on the plasma membrane of the cell it's infecting (hemagglutinin) - chromosome breaches - translocation - deletion

Question 57

Cytocidal virus effects:

Answer 57

Question 58

What is characteristic of non-cytocidal viruses?

Answer 58

non-lytic infections where the virus replicated within the cell without killing it or causing clinical pathology

Question 59

What are viral oncogenes? How are they derived? How do they affect host cells?

Answer 59

viral genes that transform a normal cell into cancer cells that can grow and multiply indefinitely from host cell genes then incorporated into the viral genome to induce mutations interfere with the host cell growth and multiplication genes, which causes the host cells to lose the ability to control division and multiply indefinitely

Question 60

The viral ____ play(s) a role in attaching a virion to the host cell. a. envelope b. capsid c. core d. A and B

Answer 60

D

Question 61

Which statement is true about viral shapes? a. all have a round shape b. cannot have a long shape c. don't maintain any shape d. vary in shape

Answer 61

D

Question 62

Which statement is true of reverse transcriptase? a. it's a nucleic acid b. it infects cells c. it transcribed RNA to make DNA d. it is a lipid

Answer 62

C