L7 Flashcards
1
Q
- Herpes Simplex Virus Type 1 (HSV-1)
- family
A
Alphaherpesviridae
2
Q
*Herpes Simplex Virus Type 1 (HSV-1)
genome
A
dsDNA
3
Q
*Herpes Simplex Virus Type 1 (HSV-1)
virion
A
Enveloped
4
Q
*Herpes Simplex Virus Type 2 (HSV-2)
Family
A
Alphaherpesviridae
5
Q
*Herpes Simplex Virus Type 2 (HSV-2)
genome
A
dsDNA
6
Q
*Herpes Simplex Virus Type 2 (HSV-2)
virion
A
Enveloped
7
Q
Cytomegalovirus family
A
Betaherpesviridae
8
Q
Cytomegalovirus genome
A
dsDNA
9
Q
Cytomegalovirus virion
A
Enveloped
10
Q
Epstein-Barr virus
family
A
Gammaherpesviridae
11
Q
Epstein-Barr virus
genome
A
dsDNA
12
Q
Epstein-Barr virus
virion
A
Enveloped
13
Q
Human Papillomavirus
family
A
Papillomaviridae
14
Q
Human Papillomavirus
genome
A
dsDNA
15
Q
Human Papillomavirus
virion
A
nonEnveloped
16
Q
Alphaherpesvirus Variable
A
host range
17
Q
Alphaherpesvirus Short
A
reproduction cycle
18
Q
Alphaherpesvirus Rapid spread in
A
culture
19
Q
Alphaherpesvirus Efficient destruction of
A
infected cells
20
Q
Alphaherpesvirus Capacity to establish
A
latency in sensory ganglia
21
Q
Alphaherpesvirus Infection
A
HSV-1 Oral-oral, oral-genital Nearly 2/3 adults are seropositive HSV-2 Primarily genital-genital, oral-genital also possible More prevalent with sexual activity Approximately 1/5 adults are infected Primarily infect epithelial cells in the skin or mucosa; mucosa are more susceptible
22
Q
Alphaherpesvirus Incubation
A
HSV-1&2: 2 – 14 days, typically 4 – 5 days
23
Q
Alphaherpesvirus Symptoms
A
Flu-like, includes localized lesions (virus spreads to neighboring cells primarily)
Only 1/3 show symptoms
Asymptomatic can still transmit
Last for 8 to 12 days
24
Q
Alphaherpesvirus Latency
A
Stationary cells, genome circularizes and stays as an episome in the nucleus
Peripheral ganglia common site of latent infections
Triggers: sunburn, systemic infection,immune impairment,stress
25
Cell mediated immune response required
| Alphaherpesvirus
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People unable to produce antibodies can still handle herpesvirus infections
T lymphocytes detect antigens presented by MHC class I or II proteins
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26
Alphaherpesvirus Modulation of the immune response
Viral proteins bind antibodies and complement proteins
| Counter effects of interferon
27
Alphaherpesvirus Prevention
Avoid contact (e.g., kissing, sex) during active herpes recurrence
28
Alphaherpesvirus treatment
Acyclovir can be used to limit virus replication
| Will not eliminate latent infections
29
Betaherpesvirus
Restricted host range
Long reproductive cycle
Slow progression in cell culture
30
Betaherpesvirus Enlargement of
infected cells (cytomeglia)
31
Betaherpesvirus
Carrier cultures
Latent infection in a variety of tissues
Prototypical member: Cytomegalovirus (CMV)
32
Gammaherpesvirus key characteristics
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Restricted host range
Targets T & B lymphocytes
Lytic infections
Latency in lymphoid tissues
Prototypical member: Epstein-Barr virus (EBV)
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33
Beta/gammaherpesvirus Disease (Cont.)
EBV associated carcinomas
34
Burkett's lymphoma
| Beta/gammaherpesvirus Disease (Cont.)
Most common childhood cancer in equatorial Africa
Tumor in jaw, eye socket, ovaries
In all cases, tumor cells have monoclonal EBV episome
Role of EBV still not understood
Spur B cell growth, mutations, or
Genes transform cells
35
Beta/gammaherpesvirus Disease
EBV associated carcinomas (Cont.)
| Hodgkin’s lymphoma
36
Hodgkins lymphoma
Three types
NL – nodular sclerosing
MC – mixed cellularity
LD – lymphocyte depleted
EBV present in 60% to 90% of MC & LD tumors, 20% to 40% of NL tumors
Exact role of EBV unknown
37
Antiviral Host Response
| Intrinsic
Block cell death
| Inhibits apoptosis
38
Antiviral Host Response
| Innate
Decrease NK cell activity
| Inhibit NK receptor activation
39
Antiviral Host Response
| Adaptive
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Decreased antigen presentation
Degrade MHC class I & II
Blocks MHC class II and T-cell receptor interactions
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40
Beta/gammaherpesvirus Disease CMV
Persist in hematopoietic progenitor cells and macrophages in vitro
Chronic persistent infection, not latency
Controlled by healthy, active immune system
41
EBV
Persistence of genome in memory B cells
| Virus proteins ensure B cell proliferation and EBV genome replication
42
Infections are usually
| Beta/gammaherpesvirus Treatment & Prevention
self limiting in immune competent individuals
43
Beta/gammaherpesvirus Antiviral therapy
Recommended for disseminated CMV & EBV in immune compromised individuals
Ganciclovir, foscarnet, acyclovir:
Inhibits viral genome replication
Resistance can develop during therapy
Less effective treating EBV induced lymphoproliferation, genome replication not essential for viral gene expression
44
Beta/gammaherpesvirus Antiviral therapy
Prophylactic or preemptive treatment, common in transplant patients
45
Immunoprophylaxis
| Beta/gammaherpesvirus
Passive transfer of antibodies for prevention of CMV infection
Transfer of EBV-specific T lymphocytes
46
Human Papillomavirus family
Papillomaviridae
47
Human Papillomavirus genome
circular dsDNA
48
Human Papillomavirus virion
non-enveloped
49
Human Papillomavirus Biology -Gain access through
abrasion of the skin
50
Human Papillomavirus Biology -Establish infection in
basal layer
51
Human Papillomavirus Biology -Cell polymerase required for
genome replication
52
Human Papillomavirus Biology -Virus production in
differentiating cells
53
Human Papillomavirus Biology -Non-lytic, virus released with
dead cell shedding
54
Human Papillomavirus Disease infection
```
direct skin-to-skin contact, fomites
Normal skin is a very strong barrier
Mucous membranes more susceptible
Virus enter body through abrasions
Virus is hardy to environmental stresses; allows transmission via fomites
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55
Human Papillomavirus Disease (Cont.) symptoms
Site of infection
Take months to manifest
Warts – raised or flat
~50% regress on their own in 2 years
56
HPV disease Respiratory papillomatosis
Rare complication
Respired virus
Can be lethal
57
HPV diseas Oncogenesis – cervical cancer
HPV requires actively replicating cells to replicate and produce progeny
E7 blocks retinoblastoma (Rb) protein – continued cell proliferation
E6 blocks the p53 tumor suppressor pathway
Actual path to cancer unknown
Viral transformation
Cell proliferation leading to cancerous mutation
58
HPV Most treatments
ablative
Liquid nitrogen, surgical excision, laser, caustic chemicals
Treatments may have to be repeated
59
HPV No proof that condoms
reduce risk
60
HPV Vaccination
Gardasil (Merck) – protects against HPV-6, 11, 16, and 18
61
Antiviral Therapy Antivirals block
specific steps in the virus life cycle
62
Antiviral therapy Must be active against
virus replications, but not normal cellular function to reduce toxicity
63
Antiviral therapy Exploit
structural, functional, and genomic information to identify targets
64
Virus resistance to
antiviral drugs is common and requires continued development efforts
65
Antivirals preventing entry Enfuvirtide – HIV
Blocks refolding of gp41, inhibits membrane fusion
66
Antivirals preventing entry:
| Amantadine & rimantadine – influenza
Blocks influenzaion channel (M2) preventing nucleocapsid releaseat the end of the cellentry process
67
Nucleoside analogs →
chain terminators
68
Acyclovir (treatment of herpesvirus infections)
First antiviral approved for clinical use
Key hurdles for antiviral success
Specificity depends on virus thymadine kinase (TK)
Bioavailability
Most effectiveagainst HSV-1& HSV-2, lesseffective for EBV & VZV,even less effective for CMV
69
Acyclovir
like nucleoside inhibitors for herpesvirus infections
70
Ganciclovir
effective against CMV, more toxic due to interference with cellular kinases
71
Valganciclovir
activity similar to acyclovir, improved oral bioavailability
72
Foscarnet (herpesvirus treatment)
Prevents viral polymerase activity
IV administration
Toxic
73
Antivirals preventing genome replication
Nucleoside inhibitor of RNA viruses
74
Antivirals preventing genome replication ribavirin (many mechanisms)
Triphosphate form inhibits polymerases
Monophosphate form inhibits inosine monophosphate dehydrogenase lowering GTP in cell
Impairs capping of mRNA
75
Antivirals Preventing Viral Proteases
Maturation of progeny viruses often requires
cleavage of virus polypeptide
76
Antivirals Preventing Viral Proteases Immature progeny are not
infectious
77
Antivirals Preventing Viral Proteases - Example: ritonavir (treatment of HIV)
Blocks cleavage of Gag-Pol polypeptide
“Boosts” activity of other protease inhibitors because it also blocks the action of cellular proteases that act on other viral protease inhibitors
78
Antiviral Challenges - Bioavailability
Absorption into the body
Transport to site of viral infection
Intake by cell
Therapeutic window (half-life)
79
Antiviral Challenges - Specificity
Targets the virus activities exclusivelyor with great preference
80
Antiviral Challenges - Toxicity
Low impact on patient
81
Natural antivirals Interferons
Fortuitous discovery by Isaacs & Lindenmann
Noted that cultured cells infected with one virus were resistant to infection by a second virus
Effect was transferable to uninfected cells
Identified proteins responsible for the effect
82
Interferons Mechanism of action
not well understood
| More effective against RNA viruses than DNA viruses
83
Vaccines Term vaccination started
with Dr. Edward Jenner in 1801 with a publication of his findings for smallpox vaccination
84
Vaccines founding
Milkmaids who had cowpox, could not under variolation (skin inoculation with smallpox)
Performed experiment in 1796 on young man demonstrating cowpox infection (vaccine virus) was protective against smallpox infection
Vaccination became the preferred method because it was much less severe
85
Active immunization –
administering all or part of a pathogenic agent to induce antibodies or cell-mediated immunity
86
Passive immunization –
administration of exogenously produced antibodies
87
Vaccines - Two forms:
live, attenuated; killed
88
Vaccines Reversion –
possible complication with live, attenuated vaccines
89
Vaccine-acquired paralytic poliomyelitis (VAPP)
1:1,000,000 to 3,000,000 of vaccinations
Local epidemics where used
Because rate of polio is so low in the US, only the killed vaccine is used
90
Vaccines utilizing B cell and T cell immunity including
secretory IgA
| Influenza, polio, oral typhoid
91
Vaccine considerations
Age
Young children & the elderly
Weaker immune systems
May not be able to respond to live, attenuated vaccines
Special populations
Immunocompromised persons may have greater need of vaccination or be counter-indicated for vaccination
Complications – for example, smallpox vaccine for persons with eczema
