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SMP - MIM Part 2 > Lecture 10 - Properties of Viruses > Flashcards

Lecture 10 - Properties of Viruses Flashcards

1
Q

What is a virus? What to note?

A

Acellular organism with nucleic acid genome that enters a living host and replicates using host biosynthetic machinery

NOTE” “virus” refers to the entire biology and is not limited to the virus particle

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2
Q

3 key characteristics of viruses? What to note?

A
  1. No metabolism (they cannot produce energy)
  2. No protein synthesis machinery
  3. Replication involves de novo assembly of new infectious particles that transport the viral genetic material to another host cell or organism

NOTE: 1 + 2 = cells that they infect must be living, so dead cells on our skin are a barrier to viruses

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3
Q

Other name for virus particle?

A

Virion

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4
Q

What is a virus particle?

A

An infectious package of genetic material

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5
Q

Describe the genome of a virus particle.

A
  1. RNA or DNA
  2. Multiple topologies: single stranded, double stranded, linear, circular, segmented
  3. Characteristics are specific for each virus type (e.g. all influenza viruses have segmented single stranded RNA genomes)
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6
Q

How do RNA viruses replicate their genome? What to note?

A

They use a virally encoded RNA-dependent polymerase (therapeutic target, e.g. Hep C drugs)

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7
Q

Which mutate more rapidly: RNA or DNA viruses? Why?

Implications?

A

RNA viruses because RNA polymerase does note have proof-reading activity

Implications:

  1. Limits genome size
  2. Better immune avoidance
  3. Better drug-resistance
  4. Cross-species infection due to better adaptation capability
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8
Q

What are 7 examples of DNA viruses?

A
  1. Herpes viruses (HSV-1,2, Varicella, KSHV)
  2. Adenoviruses
  3. Parvoviruses (B19)
  4. Hepatitis B virus
  5. Papilloma viruses (HPV-16,18…)
  6. Polyomaviruses (BK, JC)
  7. Molluscum contagiosum
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9
Q

What are 7 examples of RNA viruses?

A
  1. HIV
  2. Rhinoviruses
  3. Norovirus
  4. Measles
  5. Respiratory syncytial virus
  6. Influenza
  7. Hepatitis C virus
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10
Q

Example of DNA virus with small genome?

A

HPV

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11
Q

2 roles of the shell of a virus particle?

A
  1. Protects the genome

2. Delivers the genome to new cells

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12
Q

2 types of virus particle shells? Examples for each?

A
  1. “Naked” capsid with icosahedral nucleocapsid = protein only (e.g. rhinovirus, enteroviruses, polyo, D68, hepatitis A, norovirus, coxsackie virus, papillomaviruses, adenoviruses, parvoviruses)
  2. Enveloped = lipid membrane derived from the host + protein (e.g. influenza, measles, flaviviruses: hepatitis C, dengue, HIV, zika, etc.)
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13
Q

2 properties of viruses with a naked capsid? 6 consequences?

A
  1. Environmentally stable
  2. Released from the cell by lysis in most cases

Consequences

  1. Easily transmitted (fomites, from hand to hand, surfaces, dust, small droplets)
  2. Can retain infectivity even after drying out
  3. Many can survive the adverse conditions of the gut
  4. Resistant to detergents and poor sewage treatment
  5. Most kill the infected cell to release progeny
  6. Antibody may be sufficient for immunoprotection since the virus particles kill infected cells anyways
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14
Q

2 properties of viruses with an envelop? 4 consequences?

A
  1. Environmentally labile: disrupted by detergents, drying, heat
  2. Released from the cell by budding or cell lysis and some can spread directly from cell to cell

Consequences

  1. Must stay wet or else the membrane will dry out and lose its shape and will not longer be infectious
  2. Spread in large droplets, secretions, organ transplants, blood transfusions
  3. Do not need to kill the cell to spread (chronic infection)
  4. Some require cell-mediated immune responses for protection and control
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15
Q

2 types of enveloped virus particles? Examples for each?

A
  1. With icosahedral nucleocapsid (e.g. hep C, Zika, HIV, and herpes)
  2. With helical nucleocapsid (e.g. measles, respiratory syncytial virus, rabies, coronaviruses, influenza) => RNA/DNA bound to proteins
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16
Q

Difference between capsid and nucleocapsid?

A

Capsid = the viral protein that directly encases the genome

Nucleocapsid = the capsid + the genome

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17
Q

Which type of enveloped virus particles is more typical for RNA viruses?

A

Helical nucleocapsid

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18
Q

How to classify viruses?

A
  1. Virion morphology (i.e. shape, size, type of shell)
  2. Genome composition
  3. Genetic similarity (i.e. replication mechanisms)
  4. Type of Disease (e.g. hepatitis viruses)
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19
Q

Examples of viruses that are very similar genetically, but not in terms of diseases?

A
  1. Picornaviridae: rhinovirus, polio, coxsackie, hep A

2. Flaviridae: HCV (not transmitted by mosquitos), West Nile, dengue, Zika

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20
Q

How many DNA virus families infect humans?

A

8

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21
Q

How many RNA virus families infect humans?

A

17

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22
Q

What do viruses within the same family share?

A
  1. Similar morphology
  2. Similar gene organization
  3. Genetic relatedness can affect:
    - Laboratory diagnosis
    - Course of infection
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23
Q

What are the 6 steps of viral pathogenesis?

A
  1. Attachment and entry
  2. Virus replication in infected cells
  3. Spread through body
  4. Host responses to infection: innate and adaptive
  5. Effects on host cells due to virus and host response
  6. Exit
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24
Q

What is responsible for symptoms when the virus does not kill infected cells?

A

Body’s response to the virus

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25
Q

What does attachment of the virus involve? What to note?

A

Involves an interaction between a protein on the surface of the virus and a “receptor” on the surface of a target cell

NOTE: host cell receptor is a critical determinant of cell (and species) specificity => major determinant of the type of disease caused

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26
Q

2 ways a virus spreads in an infected individual? Describe each.

A
  1. Local: replication occurs near where the virus entered the body (e.g. many viruses that cause upper respiratory infections; papillomaviruses)
  2. Systemic: transit from the entry point to infect target cells/tissues
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27
Q

What is a factor that causes some viruses to only spread locally in upper respiratory airways?

A

Temperature is slightly lower than the core body temp

28
Q

What are 3 examples of viruses that cause upper respiratory infections?

A
  1. Influenza
  2. Rhinoviruses
  3. Syncytial virus
29
Q

What are the 3 major mechanisms for systemic spread of virus infection within an infected person? Provide examples for each.

A
  1. Bloodstream (viremia) => polio and other enteroviruses (Coxsackie)
  2. Lymphatic system => measles and HIV
  3. Nerves => rabies
30
Q

Describe the pathogenesis of enteroviruses. How to block the spread?

A
  1. Viral entry through mouth
  2. Virus replication in tonsils and Peyer’s pathces
  3. Spread to target tissues through blood => primary viremia

Block spread by using antibodies

31
Q

How does the measles virus enter the body?

A

Respiratory airways

32
Q

What is replication associated with for viruses that cause infected cell death?

A

Replication is often associated with cytopathic effects (CPE) = morphological changes in host cells caused by virus infection:

  1. Syncytia
  2. Inclusion bodies
  3. Apoptosis
33
Q

Describe a general virus replication cycle once it has entered the cell.

A
  1. Disassembly
  2. Make genome copies
  3. Transcription and translation to make viral proteins
  4. Assembly
  5. Exit
34
Q

What happens to some of the viral proteins during a viral replication cycle?

A

Some viral proteins are presented on surface MHC I

35
Q

3 possible roles of viral proteins?

A
  1. Active in transcription and translation to make viral proteins
  2. Involved in interfering with host response (e.g. block MHC expression)
  3. Assembled into new virus particles
36
Q

4 possible effects of virus on infected cells?

A
  1. CPEs
  2. No apparent effect
  3. Latent infection
  4. Tumorigenesis
37
Q

2 viruses that cause latent infection of some infected cells?

A
  1. HIV and some polyomaviruses: infection of “quiescent” cells
  2. Herpes: specific program of gene expression
38
Q

Describe syncytia formation.

A

Fusion of membrane outside the envelop of the virus with cell envelop, as part of the entry mechanism or when they have already entered a cell and want to spread to another

39
Q

Is humoral antibody sufficient to prevent spread via syncytia formation?

A

NOPE

40
Q

Describe the formation of viral inclusion bodies. Purpose? What to note?

A

Large portions of the infected cell can become virus replication factories to:

  1. Hide from the cell to minimize innate host response
  2. Concentrate viral components to allow for more efficient replication

NOTE: inclusion bodies are visible using a regular microscope

41
Q

4 examples of viruses that form inclusion bodies?

A
  1. Rabies
  2. Adenovirus
  3. Herpes simplex
  4. Cytomegalovirus
42
Q

Describe a viral latent infection. Purpose?

A

Virus genome is present in infected cells but there is no active production of infectious virus particles (no replication)

Replication can be (re-)activated by specific signals

Purpose: important mechanism of virus persistence in the host as the immune system cannot detect (kill) infected cells if replication is not occurring

43
Q

2 mechanisms by which viruses can cause cancer? Examples for each? What to note?

A
  1. Direct manipulation of the host cell division mechanisms by the virus => human papillomaviruses, merkel cell virus (rare)
  2. Combinations of environmental, viral and host genetic factors => HTLV-1, HTLV-2, Kaposi’s sarcoma-associated herpesvirus, Epstein-Barr virus, HBV, HCV

NOTE: generally takes many years to develop

44
Q

What are the 2 types of host responses to infection?

A
  1. Early: local immunity with non-specific innate responses, including cytokines (IFN and others) that interfere with virus replication and produce non-specific symptoms
  2. Later: clearance of virus and subsequent protective immunity, which can be complicated by virus mutations (HCV) or subsequent infections by related viruses (Dengue, Zika) => cell killing by T-cells can produce symptoms
45
Q

What are 3 examples of viruses for which the host response may be insufficient to clear the virus?

A
  1. HIV
  2. HBV
  3. HCV
46
Q

What are 3 examples of viruses that only have one serotype and allow for the development of vaccines?

A
  1. HAV
  2. HBV
  3. Measles
47
Q

What to note about most poliovirus infections?

A

They are asymptomatic because they are cleared by the immune system before spread to the nervous system

48
Q

What is the loss of lymphoid tissues and immunological structures during HIV infections due to?

A
  1. Virus killing of infected cells
  2. Immune killing of infected cells
  3. Dysregulated immune cell activation leading to killing of uninfected cells
49
Q

Describe acute vs long-term infections? Which are more common?

A
  1. ***Acute: typically resolves within days-weeks with development of protective immune responses (90% of infections)
  2. Long-term (chronic) with:
    - Persistent replication (HBV, HCV, HIV)
    - Latency
50
Q

What are the 7 major routes of virus infections?

A

EPITHELIA

  1. Skin
  2. Conjuctiva
  3. Respiratory tract
  4. Gastrointestinal tract
  5. Genitourinary tract
  6. Parenteral (i.e. injection: HBV, HCV)
  7. Placenta
51
Q

What does the route of viral infection depend on? 3 factors.

A
  1. Physical properties of the virus
  2. Site of replication in the source (tropism)
  3. Type of infection caused by the virus (acute vs. chronic)
52
Q

6 possible viral transmission routes?

A
  1. Secretions: aerosolization, hand to mucous membranes
  2. Transcutaneous
  3. Fecal-oral
  4. Sexual
  5. Hematogenous (blood transfusions, needle sticks)
  6. Insects (mosquitoes)
53
Q

What does viral transmission depend on? Implication?

A

Modes of transmission are intimately linked to the types of cells infected and whether the infection is chronic or acute => strong relationship between transmission and disease symptoms

54
Q

3 ways to diagnose/detect viruses?

A
  1. Symptoms
  2. Direct methods
  3. Indirect methods
55
Q

4 direct methods to detect viruses?

A
  1. Cytology/histology: inclusion bodies/syncytia
  2. Virus growth in culture
  3. Virus antigen
  4. PCR (RT-PCR for RNA viruses): sensitive but requires appropriate sample and window for positive detection might be short
56
Q

1 indirect method to detect viruses?

A

Antibody: usually detectable as infection is resolving

57
Q

What are the 3 general approaches to antiviral therapy?

A
  1. Immune system modulation (indirect): interferon, ribavirin??
  2. Direct-acting antivirals: currently most useful for long-term infections (e.g. HIV, HCV)
58
Q

Issue with viral treatment using interferon?

A

Side-effects (similar to flue symptoms)

59
Q

3 challenges with using direct-acting antivirals?

A
  1. Most viruses use a small number of proteins for replication (few targets)
  2. Many RNA viruses mutate rapidly (resistance)
  3. For acute infections rapid diagnosis is critical
60
Q

Treatment for HCV?

A

Targeting replication:

  1. Processing of viral proteins by HCV NS3-4A protease
  2. Synthesis of viral RNAs by HCV NS5B polymerase
61
Q

5 ways to prevent viral infections?

A
  1. Vaccination
  2. Passive antibody administration
  3. Physical/social measures: isolation and hand-washing (esp. enveloped viruses because the envelop is sensitive to detergents)
  4. Therapy
  5. Testing the blood supply
62
Q

List 11 viruses that we have vaccines for.

A
  1. Smallpox
  2. Polio
  3. Measles
  4. Mumps
  5. Yellow fever
  6. Rubella
  7. Varicella zoster
  8. Hepatitis B
  9. Hepatitis A
  10. Human papilloma virus
  11. Influenza
63
Q

3 different types of viral vaccines?

A
  1. Live attenuated
  2. Killed virus
  3. Subunit vaccine

NOTE: also new technologies on the horizon

64
Q

What are some viruses that present challenges for vaccine development?

A

HIV, HCV, RSV, Dengue?

65
Q

What 7 viruses are blood donations tested for in the US?

A
  1. HBV
  2. HCV
  3. HIV 1
  4. HIV 2
  5. HTLV1
  6. HTLV2
  7. West Nile virus
66
Q

What 2 things to note about DNA viruses with large genomes?

A
  1. They have more complex replication

2. They have more complex host immune avoidance strategies

SMP - MIM Part 2 (13 decks)

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