Herpes Virus Flashcards
1
Q
Herpes Virus Features
A
Large Envelope, ds DNA virus. = Approx 120 - 200 nm in diameter ,
Icosahedral Capsid Symmetry -Surrounded by Lipoprotein Envelope.
2
Q
What do all herpes viruses have in common?
A
A common virion morphology.
A basic mode of replication.
The capacity to establish acute , latent and recurrent infections
3
Q
The space between capsid & envelope is called?
A
Tegument
4
Q
Tegument - purpose
A
filled by protein and enzymes , that help to initiate replication
5
Q
Herpes - life cycle
A
1) Recognition of host cell
↓
2) Attachment
↓
3) Penetration
↓
4) Uncoating-split of double stranded DNA.( Linear ds DNA )
↓
Circularisation –becomes circular
↓
5) Transcription
↓
6) Protein synthesis(α, β, γ)
↓
7) Replication - by rolling circle
↓
8) Assembly & Envelopment
9) Exocytosis- Lysis & release
6
Q
Human herpes viruses are grouped into 3 sub-families, based on difference in viral characteristics, which are?
A
Genome structure , tissue tropism , cytopathogenicity , site of latent infection
7
Q
Human Herpes Simplex type 1 & 2 and Varicella-Zoster virus ( HHV3) are part of which group?
A
α Group
- Short reproductive cycle
- Latent in sensory neurons
- Painful skin disease
8
Q
Human Herpes Simplex type 1 & 2
A
Skin lesions & other diseases
9
Q
Varicella-Zoster virus ( HHV3)
A
Varicella (Chickenpox) & Zoster
10
Q
Cytomegalovirus (HHV5) (CMV), Human Herpes virus 6 (HHV 6) and Human Herpes virus 7 ( HHV 7 )
A
β Group
- Long reproductive cycle
- Latent in WBCs
11
Q
Cytomegalovirus (HHV5) (CMV)
A
Cytomegalic inclusion disease (CID) , Disseminated diseases in immuno compromised patients
12
Q
Human Herpes virus 6 (HHV 6)
A
Roseola infantum /lymphydenopathy
13
Q
Human Herpes virus 7 ( HHV 7 )
A
Roseola infantum / febrile seizures
14
Q
Human Epstein- Barr virus (HHV4) and Human Herpes virus 8
A
γ Group
- Latent in lymphocytes
- Associated with cancer
15
Q
Human Epstein- Barr virus (HHV4)
A
Infectious Mononucleosis , Burkitt’s Lymphoma & Nasophyryngeal Carcinoma .
16
Q
Human Herpes virus 8
A
Kaposi’s sarcoma related herpesvirus (HHV8)
17
Q
Human herpes virus 1 - virus
A
Herpes simplex type 1 ( HSV -1 )
18
Q
Human herpes virus 1 - Disease caused
A
Oral , Ocular lesion , Encephalitis , Skin lesions
19
Q
Human herpes virus 1 - Site of latency
A
Neuron-Trigeminal ganglia
20
Q
Human herpes virus 1 - Transmission
A
Close contact
21
Q
Human herpes virus 2 - virus
A
Herpes simplex type 2 ( HSV- 2 )
22
Q
Human herpes virus 2 - Disease caused
A
Genital , Neonatal infection , aseptic meningitis
23
Q
Human herpes virus 2 - Site of latency
A
Neuron-Sacral ganglia
24
Q
Human herpes virus 2 - Transmission
A
Close contact , S.T.D.
25
Human herpes virus 3 - virus
Varicella Zoster ( VZV )
26
Human herpes virus 3 - disease caused
Chickenpox & herpes zoster
27
Human herpes virus 3 - site of latency
Neuron- Trig.gang
28
Human herpes virus 3 - transmission
Respiratory & Close contact
29
Alpha- herpesvirinae - primary target cell
Mucoepithelial cells – Fast-growing
30
Human herpes virus 5 - virus
Cytomegalovirus ( CMV )
31
Human herpes virus 5 - primary target cell
Leucocytes, Monocytes (M), Lymphocytes(L), Epithelial cells (EC)
32
Human herpes virus 5 - site of latency
Kidneys ; Glands Monocytes (M) Lymphocytes(L)
33
Human herpes virus 5 - means of spread
Close contact, Transfusions, Tissue transplant, Congenital, STD
34
Human herpes virus 6 - virus
Herpes lymphotropic RosealaInfantum
35
Human herpes virus 6 - primary target cell
T cells, M, L, EC
36
Human herpes virus 6 - site of latency
Lymphoid tissue ( T cells )
37
Human herpes virus 6 - means of spread
Respiratory & close contact
38
Slow-growing , ( Massive enlargment of infected cells ) .
Beta - herpesvirinae
39
Human herpes virus 7 - virus
RK virus
40
Human herpes virus 7 - primary target cell
T cells
41
Human herpes virus 7 - site of latency
Lymphoid tissue ( T cells )
42
Human herpesvirus 4 - virus
Epstein-Barr virus ( EBV )
43
Human herpesvirus 4 - primary target cell
B Lymphocytes & EC
44
Human herpesvirus 4 - site of latency
Lymphoid tissue (B cells)
45
Human herpesvirus 4 - transmission
Saliva ( Kissing disease )
46
Human herpes virus 8 - virus
Kaposi’s sarcoma related virus
47
Human herpes virus 8 - primary target cell
Lymphocytes and others
48
Human herpes virus 8 - transmission
Saliva
49
HHV-5 -- diseases caused
Congenital CMV infection , Infection in immuno compromised , acquired CMV infection , Mononucleosis like syndrome ( heterophil antibody - negative ) .
50
HHV-6 -- diseases caused
Roseola in infant (primary infection) , Lymphydenopathy ,
| Infection in allograft recipient - pneumonia , marrow failure
51
HHV-7 -- diseases caused
Some cases of Roseola , Febrile seizures in children
52
HHV-4 Epstein Barr virus - ( EBV ) -- diseases caused
Infectious mononucleosis ( Kissing Disease) ,Tumor including Burkitt’s lymphoma, Hodgkin’s ds , Nasopharyngeal carcinoma
53
HHV-8 Kaposi’s sarcoma -- diseases caused
Associated with Kaposi’s sarcoma
54
HSV-1 and HSV-2 -- features
- Extremely wide spread in human population
- Establishes latency in nerve cells - reactivation is common
- There are two distinct types of HSVs Type 1 & Type 2.
- Structurally & Morphologically indistinguishable
55
HSV-1 incubation period
2-12 days
56
HSV-2 incubation period
3 weeks
57
Reactivation of HSV 1 and 2 is caused by
Stress stimuli such as
UV light , Fever ,
Hormonal changes ,
Surgical trauma to the neuron.
58
Antibodies prevent reactivation (T/F)
False
59
HSV - pathogenesis
Why is HSV1 more commonly recurrent on mouth whilst HSV2 is more commonly recurrent on genitals?
HSV invades and replicates in neurons as well as in epidermal and dermal cells.
Virions travel from the initial site of infection on the skin or mucosa to the (Trigeminal ganglia - HSV-1 and Sacral ganglia- HSV-2) where latency is established.
HSV1 prefers to establish latency in Trigeminal ganglia whilst HSV2 prefers Sacral ganglia (which innervates the genitals)
Innervate - supply an organ with nerves
60
Acute Gingivostomatitis, Herpes Oro-labialis infection ,
Oropharyngeal infections
61
Acute Gingivostomatitis occurs in early childhood (T/F)
True
62
Acute Gingivostomatitis - symptoms
Fever , painful vesicular lesions on gums , lips & oral mucosa ,
these vesicles may rupture leaving a red based ulcer
63
Herpes Oro-labialis infection - symptoms
Milder recurrent form
Crops of vesicles at the mucocutaneous junction of lips or nose:
64
Corneal ulcers & lesions of conjunctival epithelium
Herpetic Keratoconjunctivitis
65
Dendritic ulcer or vesicles on the eye lids
Recurrent Herpetic Keratoconjunctivitis
| -- Can lead to blindness
66
Diseases caused by HSV-1
```
1- Oropharyngeal infections :
2- Herpetic Keratoconjunctivitis
3- Encephalitis :
4- Herpetic Whitlow : fingers
5- Eczema Herpeticum:
6. Meningitis
```
67
Encephalitis is more common (T/F)
True
68
Encephalitis involves where? How high is mortality?
Involves temporal lobe with high mortality.
69
PCR assay for viral DNA in CSF for which viral infection?
Encephalitis
70
Herpetic Whitlow also called
Fingers herpes infection
71
Who mostly contracts Herpetic Whitlow?
Healthcare workers, Dentists
72
Genital Herpes - transmission
Sexual contact
73
Genital herpes - symptoms
Vesiculo ulcerative lesions ( painful multiple ) of cervix , vulva , vagina , & perineum of females & On Glans or shaft of penis in males .
74
Neonatal herpes - transmission
Acquired in utero , during , or after birth
75
Severe in the newborn so , pregnant females with recurrent herpes should deliver by C .S . - which viral infection?
Neonatal herpes
76
Specimen - Herpes virus
Vesicular fluid (from vesicles) - Corneal scrapping , Skin swab .
77
Lab ID methods
Light Microscopy
Tzanck smear
Giesma stained smear
78
Tzanck smear - describe method + results
- - Smear prepared from scrapping from the base of vesicles are stained with 1 % aq. soln. of Toluidine Blue O.
- - Multinucleated giant cells with faceted nuclei & homogenously stained ‘ground glass’ chromatin
-- Tzanck cells seen
79
Giesma stained smear -
Intranuclear Cowdry type A inclusion bodies
80
Direct immunofluorescence
Cell scrapings from lesions -- stained with monoclonal antibodies with a fluorescence dye.
Viral inclusion bodies appear in microscope as a bright green Intra nuclear particles
81
Most appropriate test to confirm the diagnosis of HSV
Polymerase Chain Reaction ( PCR ) Assay
82
For detection of viral DNA ( genome ) in CSF ,vesicular fluid , skin scraping
Polymerase Chain Reaction ( PCR ) Assay
83
Tissue culture - Herpes Virus
Grown in human embryonic fibroblasts , Hep-2 cells or HeLa cells .
84
Result - culture
( CPEs ) - Swollen rounded cells ( enlarged & appear ballooned ) appear within 1-3 days . Fusion of infected cells results in syncytium formation .
85
What is serology mainly used for with respect to Herpes Virus?
Epidemiological studies
86
Serological methods - Herpes Virus
Ab (IgM) detection by ELISA , RIA and Western blot Test .or Complement FixationTest (CFT) .
87
TORCH
( Toxoplasmosis ; Other –(Varicella) ; Rubella ; Cytomegalovirus & Herpes simplex ) in pregnant women
88
Acyclovir - MoA and administration
Inhibits viral DNA polymerase enzyme.
Topical , Oral or IV.
89
Acyclovir affects latency.
Does not affect latency.
90
Drug of choice for acyclovir resistance cases
Foscarnet
91
Prevention - genital herpes
Avoid contact with individual with lesion .
| Safe sexual practice. Use of condom
92
Varicella
Chickenpox
93
Zoster
Shingles
94
Prevalence rate - varicella
Highly communicable , with an attack rate of 90% in close contacts
95
Shingles occurs regularly (T/F)
False, it occurs sporadically
96
Shingles reservoir
Humans only
97
Where does reactivation of varicella zoster virus begin in adults?
reactivation of latent VZV present in trigeminal ganglia in adult life
98
Varicella - transmission
Airborne droplets & direct contact from varicella patients
Vesicular fluid of Zoster patients - in susceptible child
99
Pathogenesis - VZV
VZV infects the mucosa of the upper respiratory tract
Multiplies in the regional Lymph Nodes .
Primary viremia and spread to liver and spleen.
Secondary viremia follows with viral spread to the skin.
Typical rash occurs ( Centripetal distribution - highest on Trunk ) .
VZV remains latent in neurons of trigeminal ganglia for life.
100
Incubation period - Varicella
10-14 days
101
Symptoms - Varicella
Mild fever & rash
102
Rash - Varicella
First appear on Face & Trunk , spread rapidly to extremities
103
Rash formation process
Flat macules become papules, then vesicles followed by crust formation.
The crust is often shed off and heals without scarring.
104
Does cropping occur in varicella?
Characteristic feature of varicella rash , fresh vesicles appear in crops/groups , so all the stages can be seen simultaneously.
105
Reactivation for latent vzv
When the vesicles reactivate, intensive pains occur
106
VZV affecting eyes and face
Keratitis , Conjunctivitis & Iritis.
107
Bell's Palsy
- - causes a temporary weakness or paralysis of the muscles in the face.
- - can occur when the nerve that controls your facial muscles becomes inflamed, swollen, or compressed.
108
Zoster of the seventh nerve ganglion can cause?
Bell's Palsy
109
The clinical presentations of varicella or zoster are so characteristic that laboratory confirmation is rarely required (T/F)
True
110
Specimen for Varicella / Zoster
Smears from vesicular lesions , respiratory secretions .
111
Direct Virus Demonstration
Light Microscopy: Tzanck smear
Cytology: Cowdry’s A type intra nuclear inclusion bodies (Giemsa Stain)
Direct Immunofluorescence: Viral inclusion bodies in microscope - bright green + intranuclear
PCR: detection of viral DNA
112
Serology tests
Specific VZV Abs using ELISA ; CFT or Neutralisation test
113
Neutralization test
Used to quantify the titer of neutralizing antibody for a virus.
Serum antibody sample to be tested is diluted and mixed with a viral suspension.
This is incubated to allow the antibody to react with the virus.
114
DOC for vzv
Acyclovir , Famciclovir or Valacyclovir
115
Acyclovir does not affect Latency of vzv (T/F)
True
116
Prevention methods
1. Active immunization-
Live attenuated varicella vaccine Single dose .
Children aged : 1- 10 years .
2. Passive immunization-
Varicella Zoster Immunoglobulins ( VZIG )
Given to:
- - Immuno compromised children exposed to infection.
- - Mothers infected near term ( before delivery ) and their infants ( immediately after delivery).
117
Infection Control Measures
Patients infected with VZV should be kept in isolation ( Airborne & Contact Precautions )
118
Largest virus in Herpesviridae family is?
Cytomegalovirus - Size = 150 – 200 nm
119
Effect of Cytomegalovirus in host cells
- Causes massive enlargement of infected host cells
120
How does Cytomegalovirus present in healthy adults?
Asymptomatic infection
121
High risk group for Cytomegalovirus
- Organ transplant patient .
| - HIV patients
122
Congenital CMV infection does not pose serious effect on foetus or new borne (T/F)
False; Congenital CMV infection may be fatal to foetus or new borne.
123
CMV transmission
in utero , perinatally or post natally
124
Infectious virions appear in urine & saliva from time to time (T/F)
True
125
CMV - mode of transmission
1- Close contact with most body fluids ( Saliva , urine , vaginal secretions & semen ).
2- Transplacental & Perinatal Transmission (Secondary to exposure to Infected birth canal ) & Breast feeding .
3- Sexually through semen & cervical secretions .
4- Blood transfusion .
5- Organ transplantation
126
Pathogenesis of CMV
First infects upper respiratory tract And lymphocytes .
During their circulation lymphocytes spread the virus to other lymphocytes & monocytes in spleen & lymph nodes.
Finally spread to a variety of epithelial cells of salivary glands , kidney tubules , testes & cervix.
127
What viral response maintains virus in latent state?
The virus elicits both humoral & cell mediated response that maintains virus in latent state.
128
Latent virus can reactivate with immunosuppression (T/F)
True
129
Congenital CMV
Perinatal (before and after birth)
Postnatal (after birth)
130
Immunocompromised CMV
- Transplant patients
- Cancer patients- chemotherapy
- HIV patients
131
CMV can cause mononucleosis type symptoms (T/F)
True
132
CMV mononucleosis type symptoms are the leading cause of morbidity and mortality
True
133
Heterophil Antibody Test- positive for CMV mononucleosis symptoms
( Heterophil Antibody Test- Negative )
134
Cytomegalic Inclusion Disease (CID)
Series of signs and symptoms caused by cytomegalovirus infection, toxoplasmosis or other rare infections such as herpes or rubella viruses.
It can produce massive calcification of the central nervous system, and often the kidneys.
Intrauterine infection :– Congenital CMV Infection -> Death
Hepatospenomegaly
Jaundice
Thrombocytopenic purpura (abnormal decrease in platelets)
Hemolytic anaemia (RBCs destroyed faster than they are made)
Microcephaly
Cerebral calcifiaction
High mortality
Mental retardation
135
Direct Virus Demonstration - CID
Light microscopy - Giemsa stain -- owl's eye cells; large, multinucleated
Direct immunofluorescence and ELISA -- finding antigens
PCR (most rapid + sensitive) & Nucleic Acid Hybridization -- Finding CMV DNA
136
Serology - CID
Panel of tests for TORCH
137
Culture - CID
Sample used is throat washing & urine . CMV grows in human fibroblast cell culture
After 3-5 weeks CPE{ Cyto- Pathic- Effect} with small foci of swollen transluscent cells with large intranuclear inclusions.
138
Ganciclovir - CID
Inhibits viral DNA polymerase enzyme
Intravenous route
DOC
139
Other drugs for CID
Valganciclovir (orally -- immunocompromised) and Foscarnet (resistant)
140
Gangiclovir does not affect CID latency (T/F)
True
141
Prevention + control -- CID
Good hygienic personal practice , careful hand washing after contact with diapers or oral secretions .
Safe sexual practice including usage of condom reduces transmission .
Isolation of infected new borne .
Screening of transplant donors & recipient for CMV antibodies .
142
Etiological agent
Materials known or reasonably expected to contain a pathogen
143
Etiological agent of infectious mononucleosis
Epstein Barr Virus
144
Which cells does EBV infect?
Infects lymphoid cells - B lymphocytes
145
EBV transmission
Saliva ( kissing disease ).
Rarely by blood or marrow transfusion . By
Sharing contaminated - Glasses , Cups & Tooth brushes.
146
Infectious mononucleosis - symptoms
High fever , sore throat , headache , myalgia , nausea & abdominal pain
Also associated with: pharyngitis , generalized lymphadenopathy , hepatosplenomegaly and fatigue
147
EBV Associated tumors/malignancies
Burkitt’s lymphoma – Africa - childhood (swelling of jaw - affects B lymphocytes).
Lymphoma – (Post –transplant lymphomas) in immunodeficient patients.
Nasopharyngeal carcinoma - Asia-Chinese.
Hodgkin’s lymphoma (non-painful enlarged lymph nodes in the neck, under the arm, or in the groin - affects WBCs)
148
Burkitt’s lymphoma
Cancer starts in immune cells called B-cells - fast growing human tumor
149
Post-transplant lymphoma
Can be a result of both solid organ transplant (kidney, lung, heart, liver, lung) and allogeneic bone marrow or stem cell transplants
150
Nasopharyngeal carcinoma
Rare tumor of the head and neck which originates in the nasopharynx
151
Hodgkin’s lymphoma
Cancer originates from a specific type of white blood cells called lymphocytes
152
Infectious mononucleosis - pathogenesis
Replicates in nasopharyngeal epithelium .
Spreads to salivary glands & oropharyngeal lymphoid tissue .
Further replication results in viraemia with subsequent infection of reticuloendothelial system , liver , spleen and B lymphocytes.
Host immune response include Cytotoxic T Lymphocytes (CTLs) - Characteristic Atypical Lymphocytes found in peripheral blood (whole blood).
153
How do this virus cause tumors?
DNA becomes integrated with the host chromosome giving the infected cell the ability to proliferate indefinitely resulting in malignancy / tumor .
154
Pathogenesis - EBV
Downey cells (abnormal lymphocytes) seen
155
Samples - EBV
Saliva , peripheral blood (P.S.) & lymphoid tissue
156
Tests EBV
Direct immunofluorescence
PCR and Nucleic Acid Hybridization :- For detection of viral DNA , most sensitive .
157
Direct immunofluorescence
Cell scrappings from lesions are stained with monoclonal antibodies conjugated with a fluorescence dye . Viral inclusion bodies appear in Microscope as a Bright Green Intranuclear particles
158
Monospot test ( horse RBCs ) / monospot test
Heterophil antibodies have the ability to agglutinate red blood cells of different animal species. The Paul-Bunnell test uses sheep erythrocytes( RBCs)
159
Serology - EBV
A) Detection of Non-specific Heterophil Antibodies:
Patients with Acute Infectious Mononucleosis develop transient non-specific Abs that agglutinate sheep RBCs / horse RBCs.
These are detected by Paul Bunnel or Monospot tests + ve.
B) Detection of specific antibodies by ELISA , Indirect Immunofluorescence:
Presence of IgM antibody to Viral Capsid antigen (VCA) – Suggest Acute Primary Infection . High IgG antibodies to VCA - Seen in Burkitt’s lymphoma , Nasopharyngeal carcinoma & Past infection .
