4.41 Flashcards
1
Q
Human Herpesviruses
characteristics (3)
A
Double-stranded DNA genome
enveloped
Genome = 125,000 - 236,000 base pairs
2
Q
Herpesviridae family members share four significant biological properties: (4)
A
- Encode a large array of enzymes involved in
- Synthesis of viral DNAs and capsid assembly occur in the nucleus, while
final processing of virions occurs in the cytoplasm - Production of virus results in destruction of the infected cell
- Able to exist in a latent state in their natural hosts while retaining the
capacity to replicate and cause disease upon reactivation
3
Q
- Encode a large array of enzymes involved in (3)
A
a. nucleic acid metabolism (thymidine kinase,)
b. DNA synthesis (DNA polymerase)
c. protein processing (protein kinases)
4
Q
Alpha
herpesviruses (3)
A
HSV1
HSV2
VZV
5
Q
Beta
herpesviruses (3)
A
cytomegalovirus
HHV6
HHV7
6
Q
Gamma
herpesviruses (2)
A
EBV
HHV8
7
Q
HSV1
A
fever blisters
8
Q
HSV2
A
sexually transmitted genital lesions
9
Q
VZV (HHV3)
A
chicken pox and shingles
10
Q
HHV5, 6, 7
A
roseola
11
Q
EBV (HHV4)
A
infectious mononucleosis
12
Q
virus: HSV1
means of transmission
portal of entry
A
direct contact
mucous membranes, skin
13
Q
virus: HSV2
means of transmission
portal of entry
A
direct contact
mucous membranes, skin
14
Q
virus: VZV
means of transmission
portal of entry
A
inhalation, direct contact
respiratory tract, mucous membranes
15
Q
virus: CMV
means of transmission
portal of entry
A
saliva, blood
bloodstream, mucous membranes
16
Q
virus: EBV
means of transmission
portal of entry
A
saliva, blood
mucous membranes, bloodstream
17
Q
Herpes viruses are fragile (enveloped) susceptible to (3)
A
heat, detergent, drying
18
Q
Generally require direct —
— more susceptible than skin
A
inoculation
mucous membranes
19
Q
CMV and EBV can be transmitted through
A
infected leukocytes
20
Q
VZV is mostly transmitted by —
A
aerosols
21
Q
Herpesvirus
Lytic cycle
Cascade of gene expression (3)
A
Attach to and infect adjacent cells upon release Budding directly onto and into adjacent cells Therefore get a local spread of virus (predominantly) Syncytia can form
22
Q
Virus replicates and assembles in the cell nucleus
Get changes in nuclear structure -
A
chromatin shifted to margins of nucleus
Cowdry type A acidophilic intranuclear inclusion bodies
23
Q
Stained cells infected with a herpes virus show — formation (multinucleated
cells) (= Tzanck cells from Tzanck smear (scraping from the base of the lesion) and
- – (darkly staining nuclear region)
A
syncytia
intranuclear inclusion bodies
24
Q
Host defenses promote recovery from primary disease
— antibodies play minor role in recovery from primary disease and on recurrent disease
But anti-herpesvirus antibodies can help prevent
A
Anti-herpesvirus
primary disease: VZV vaccine is effective
25
Host response to alpha-herpesvirus infections (HSV-1, HSV-2, and VZV)
Cell-mediated immune mechanisms play the major role in recovery
MHC class I and II proteins displaying viral antigens on surface of infected cell
activate T lymphocytes (2)
directly kill the infected cell or
| secrete cytokines and chemokines to attract macrophages, etc
26
Cell-mediated immune response varies with --- (2)
age
neonates: problems with HSVs;
elderly: problems with VZV
27
Immune evasion by herpesviruses
HSV-1, HSV-2, and VZV envelope glycoproteins bind Fc domain of antibodies and
complement components, blocking their ability to promote an antiviral response
28
HSV proteins reduce
type I interferon production and its downstream signaling
| pathway
29
HSV proteins can prevent
```
MHC class I and II proteins from being expressed on the
surface of infected cells
```
30
Latency results in
no expression of viral proteins and therefore no peptides for
MHC proteins to display
31
1. Acute disease (4)
facial or genital herpes, stomatitis, or keratitis
| localizied
32
```
1. Acute disease
Exposure of (4)
```
skin, mucosa, or cornea to secretions
| containing virus
33
1. Acute disease
Replication of virus in epithelial cells, causing
(3)
vescular mucocutaneous lesions, stomatitis, or
| keratitis
34
```
1. Acute disease
Spread to (2)
```
peripheral sensory or autonomic nerve
| endings and ganglia
35
1. Acute disease
HSV-1 acquired ---
--- of adults are Ab+
very early in life (e.g. kissing)
| 2/3
36
1. Acute disease
HSV-2 mostly transmitted by ---
--- of adults are Ab+
genital contact
uncommon before adolescence
1/5
37
1. Acute disease
Most HSV-1 and HSV-2 infections are ---
~--- of infections have recognizable symptoms
asymptomatic
| 1/3
38
Usual Course of Herpes Simplex Virus Infection and Disease (continued)
2. Recovery
Healing of lesions and establishment of latent
| infections in neurons
39
Usual Course of Herpes Simplex Virus Infection and Disease (continued)
3.
Latency Maintenance of latent infections in neurons
40
Usual Course of Herpes Simplex Virus Infection and Disease (continued)
4. Recurrent disease (4)
cold sores, fever blisters, keratitis, or genital lesions
localizied
Reactivation of latent virus and distal spread
Recurrent lesions caused by virus replication in
epithelial cell
41
reactivation of various herpesviruses
| can be induced by: (6)
```
Local trauma (surgery or nerve pressure)
Mental tension
Fatigue
Menstruation
Exposure to bright light
Aging effects
```
42
```
infection: occular herpes
predominant virus type:
frequency:
age group:
usual outcome:
recurrence:
```
```
1
common
all
resolution, visual impairment
yes
```
43
```
infection: oral herpes
predominant virus type:
frequency:
age group:
usual outcome:
recurrence:
```
```
1>2
very common
all
resolution
yes
```
44
```
infection: genital herpes
predominant virus type:
frequency:
age group:
usual outcome:
recurrence:
```
```
2>1
common
adolescents, adults
resolution
yes
```
45
Herpes keratitis -
eye (can lead to scarring/blindness)
46
most common viral infection of the mouth
Herpetic stomatitis
47
Herpetic stomatitis
Primary infection by (2)
vesicles on (3)
HSV-1 or HSV-2
| oral mucosa, the tongue, and gingivae
48
Herpetic stomatitis -
| confused with --- when gingivae inflamed
acute necrotizing ulcerative gingivitis (ANUG)
49
Herpes labialis (cold sore) -
reactivation of latent HSV-1 or HSV-2
50
VZV (HHV-3) (2)
chicken pox
| shingles
51
VZV
| --- transmission (---% of adults have VZV antibody (from time before vaccination)
Aerosol
| 90
52
VZV
| Local viral replication in ---
respiratory tract
53
VZV
| Virus progresses to phagocytic cells via the (2)
bloodstream and lymphatic system
54
VZV
| --- spreads the virus throughout the body, including the skin
Secondary viremia
55
```
VZV
Secondary viremia spreads the virus throughout the body, including the skin
occurs --- days post infection
skin lesions appear over the ---
systemic spread is different from ---
```
11-13
entire body
herpes simplex viruses
56
VZV
| Virus spreads cell-to-cell like ---
HSVs
except epithelial cells of lung keratinocytes and skins lesions, which can release virus
57
VZV replication is similar to HSVs but ---
| 2
slower [smallest genome of HHVs (~125,000 bp)]
also establishes latent infection of neurons
dorsal root ganglia or cranial nerve ganglia
58
VZV reactivated in older adults with impaired --
cell-mediated immunity
59
VZV reactivated in older adults with impaired cell-mediated immunity
virus is released along the entire --- pathway to infect the skin
neural
60
VZV reactivated in older adults with impaired cell-mediated immunity
causes a vesicular rash along the entire dermatome =
herpes zoster or shingles
61
VZV reactivated in older adults with impaired cell-mediated immunity
postherpetic neuralgia in ---% of older patients
pain for --- after zoster
30
| months to years
62
Dermatome is area of skin
| innervated by
fibers from a single
| dorsal root spinal nerve
63
Host defenses promote recovery from primary disease
- -- play minor role in recovery from primary disease and on recurrent disease
- -- mechanisms play the major role in recovery as for HSVs
Anti-VZV antibodies
| Cell-mediated immune
64
Anti-VZV antibodies play minor role in recovery from primary disease and on
recurrent disease
But anti-VZV antibodies can help prevent ---
And anti-VZV antibodies limit --- spread of virus
primary disease
VZV vaccine is effective
viremic
65
Childhood illness = ---
Chickenpox
66
Primary infection of adults more severe
| can cause
interstitial pneumonia in 30% of adults and may be fatal
67
Epstein-Barr virus (EBV; HHV-4)
| infects (2)
B lymphocytes and epithelial cells
68
Cytomegalovirus (CMV; HHV-5)
infects a wide variety of cells
69
EBV and CMV replication within host cells is very similar to
general description of
| herpesvirus replication given previously
70
Establishment of CMV:
persistent/chronic infection
71
Establishment of EBV latent infection (2)
latent infection in memory B cells
| virus proteins produced during latency promote B cell proliferation
72
CMV and EBV infections are very common
---% of adults in developing world
---% of adults in United States
usually --- when acquired early
95
50-60
asymptomatic
73
EBV acquired similarly, except --- not a important route of virus spread
breast milk
74
Symptomatic infections when acquired after childhood:
infectious mononucleosis
75
most common viral infection of the fetus in humans
Congenital CMV
76
Congenital CMV
| leads to
severe disease and permanent neurological damage,
| including hearing loss and learning disabilities
77
Persistent CMV and EBV infections associated with (2)
EBV: (3)
chronic inflammatory diseases and cancer
Hodgkin disease, African Burkitt lymphoma, and nasopharyngeal carcinoma
78
Diagnosis
| CMV:
large inclusions in tissue specimens (“owl eye” inclusions)
79
Diagnosis
| EBV: (2)
PCR
| heterophile antibody or “monospot” test
80
heterophile antibody or “monospot” test (2)
EBV infection induces production of large number of antibodies that recognize RBC
antigens of other species (“heterophile antibodies”)
Monospot test
81
Monospot test:
agglutination of horse RBCs by heterophile antibody in patient’s serum
82
virus: cytomegalovirus (2)
syndrome:
congenital infection
| monocucleosis
83
virus: EBV
syndrome:
mononucleosis
84
virus: herpesvirus type 6
syndrome:
roseola
85
virus: herpesvirus type 7
syndrome:
rosela
86
virus: kaposis sarcoma associate virus
syndrome:
kaposis sarcoma?
87
Oral manifestation of other herpes virus infections
| Chickenpox (VZV) -
lesions may be found in mouth before skin rash develops
88
Oral manifestation of other herpes virus infections
| Shingles (VZV reactivation) (2)
trigeminal nerve affected in 15% of cases
| Ophthalmic > maxillary > mandibular divisions involved (lesions)
89
Oral manifestation of other herpes virus infections
| Ophthalmic > maxillary > mandibular divisions involved (lesions)
```
oral pain often precedes rash and mimics toothache pain
most common intraoral sites affected:
anterior half of tongue
soft palate
cheek
```
90
Shingles (VZV reactivation)
| most common intraoral sites affected: (3)
anterior half of tongue
soft palate
cheek
91
Oral manifestation of other herpes virus infections
| Epstein-Barr virus (EBV) - infectious mononucleosis (3)
painful sore throat at onset of infection
rash may be present at junction of hard and soft palates (fine petechial hemorrhages)
White pseudomembrane may develop on tonsils and other parts of oral mucosa
92
Oral manifestation of other herpes virus infections
| HHV-8 (Kaposi’s sarcoma-associated virus)
Kaposi’s sarcoma lesions (endothelial tumor)
93
Herpesvirsuses and periodontal disease
| • (2) present in majority of advanced periodontal lesions
Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
94
Possible roles for herpesviruses in periodontal disease: (5)
1. Viruses may cause direct cytopathic effects
2. Gingival viruses may promote bacterial attachment/colonization
3. CMV and EBV can infect monocytes, macrophages, and
lymphocytes in lesions and impair cell function.
4. Viruses induce a proinflammatory response that can result in
tissue destruction.
5. Viruses can suppress host defenses locally and systemically
