Herpesviridae mycv Flashcards
- Enveloped icosahedral capsid, linear double
stranded DNA - ~120-300nm
- ____=to creep
- Virion consists of 4 components: __,___,___,___
- 3 known subfamilies __,___,___
HERPESVIRIDAE
- herpes
- nucleic acid core, capsid, tegument and envelope
- Alphaherpesvirinae-HSV type 1 and 2, VZV
➢ Betaherpesvirinae-CMV, HHV-6, HHV-7
➢ Gammaherpesvirinae-EBV, HHV-8
HUMAN HERPESVIRUS
- Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2)
- Varicella-zoster virus (VZV)
- Epstein-barr virus (EBV)
- Cytomegalovirus (CMV)
- Human herpesviruses 6 and 7 (HHV-6 and HHV-7
- HHV-8, (associated with Kaposi sarcoma)
Hallmark characteristic: ___
* Reactivation can be caused by various stimuli
* Fever, stress, UV exposure, axonal injury, immunosuppression
* Form ____
* ____ was the first human herpesvirus to be recognized
HERPESVIRIDAE
- latency
- Cowdry Type A intranuclear inclusion bodies
- Herpes Simplex Virus (HSV)
Alphaherpesvirinae
Human herpesvirus 1, 2, 3
Gammaherpesvirinae
Human herpesvirus 4 and 8
Betaherpesvirinae
Human herpesvirus 5, 6, 7
Human herpesvirus 1
Virus:
Primary target cell:
Site of latency:
Mode of spread
Herpes simplex type 1
Mucoepithelial cells
Neuron
Close contact
Human herpesvirus 2
Virus:
Primary target cell:
Site of latency:
Mode of spread
Herpes simplex type 2
Mucoepithelial cells
Neuron
Close contact (std)
Human herpesvirus 3
Virus:
Primary target cell:
Site of latency:
Mode of spread
Varicella- zoster virus
Mucoepithelial cells
Neuron
Close contact and respiratory contact
Human herpesvirus 4
Virus:
Primary target cell:
Site of latency:
Mode of spread
Epstein- Barr virus
Bcells and Epithelial cells
b cell
saliva(kissing dse)
Human herpesvirus 8
Virus:
Primary target cell:
Site of latency:
Mode of spread
Kaposi’s sarcoma relaated virus
lymphocyte and other cells
n/a
close contact saliva and std
Human herpesvirus 5
Virus:
Primary target cell:
Site of latency:
Mode of spread
-cytomegalovirus
-monocyte, lymphocyte and epithelial cells
- monocyte and lymphocyte
- close contact, transfusions, tissue transplant and congenital
Human herpesvirus 6
Virus:
Primary target cell:
Site of latency:
Mode of spread
- Herpes lymphotropic virus
- tcells
- t cells
-respiratory and close contact
Human herpesvirus 7
Virus:
Primary target cell:
Site of latency:
Mode of spread
Human herpesvirus 7
t cells
t cells
n/a
- Infection of either the skin or genitalia
Herpes Simplex Virus
- * HSV type 1 (Human herpes virus type 1 or HHV type 1)
* HSV type 2 (HHV type 2)
is usually isolated from lesions in and around the mouth and is transmitted by direct contact or droplet spread from cases or carriers.
>Infections above the waist
HSV type 1 (Human herpes virus type 1 or HHV type 1)
is transmitted sexually or from a maternal genital infection to a new born.
>Infection below the waist
- HSV type 2 (HHV type 2)
PATHOGENESIS
* Initially infect and replicate in mucoepithelial cells and then establish latent infection of the innervating neurons.
* Skin and mucous membranes are the portals of entry in which the
virus also multiplies, causing lysis of cells and formation of vesicles.
* After replication is under way in the skin or a mucous membrane,
virions travel to the root ganglia via the sensory nerves supplying the
area.
Herpes Simplex Virus
a. Most common site is the face—on the cheeks, chin, around the mouth or on the forehead;
b. Napkin rash;
c. ‘fever blister’ or herpes febrilis
d. ___- an infection of the finger;
e. _____ an infection of the body;
f. Eczema herpeticum
Herpes Simplex Virus (Cutaneous Infections)
- Herpetic whitlow
- Herpes gladiatorum
Herpes Simplex Virus Oral infection
1
2
3
4
5
Acute gingivostomatitis
herpetic stomatitis
pharyngitis
tonsillitis
localized lymphadenopathy
Herpes Simplex Virus Ophthalmic
Severe keratoconjunctivitis, follicular conjunctivitis with vesicle formation on the lids,
dendritic keratitis or corneal ulcers or as vesicles on the eyelids, corneal scarring and impairment
of vision
Herpes Simplex Virus Nervous system
1
2
3
4
5
- HSV encephalitis;
- Sporadic encephalitis;
- HSV meningitis;
- Sacral autonomic dysfunction;
- Rarely transverse myelitis or the Guillain–Barre syndrome and Bell’s palsy
Herpes Simplex Virus Visceral
HSV esophagitis;
* Tracheobronchitis and pneumonitis;
* Hepatitis;
* Erythema multiforme;
* Disseminated HSV infection
Genital disease is usually
caused by ___
HSV-2
are known to increase
the risk of transmission of infection with human immunodeficiency virus (HIV).
Genital herpetic ulcers
Herpes Simplex Virus, in male patients: The lesions typically develop on __,__,
the glans or shaft of the penis, urethra
Herpes Simplex Virus, * In female patients: The lesions may be seen on the___,__,__,__,__
vulva, vagina, cervix, perianal area, or inner thigh
Herpes Simplex Virus, In patients of both sexes
Inguinal lymphadenopathy
Herpes Simplex Virus, In homosexuals;
- Herpetic proctitis
Transplacental infection with HSV1
or 2 can lead to congenital malformations
Neonatal Herpes
Herpes Simplex Virus
* Direct Detection
Electron microscopy of vesicle fluid -Immunofluorescence of skin scrapings
- PCR
Herpes Simplex Virus Virus Isolation - __ AND ___are among the easiest viruses to cultivate. It usually takes only 1 - 5 days for a result to be available
HSV-1 and HSV-2
Herpes Simplex Virus, Not that useful in the acute phase because it takes 1-2 weeks for before antibodies appear after infection. Used to document to recent infection
Serology
rapid result but cannot distinguish
between HSV and VZV
Electron microscopy of vesicle fluid
can distinguish between HSV and VZV
Immunofluorescence of skin scrapings
__ - now used routinely for the diagnosis of herpes simplex encephalitis and other herpes simplex infections
PCR
Herpes Simplex Virus TREATMENT
Acyclovir
Famciclovir and valacyclovir –
Other older agents – e.g. idoxuridine, trifluorothymidine, Vidarabine (ara-A)
These agents are highly toxic and is suitable for topical use for ophthalmic
infection only
idoxuridine, trifluorothymidine, Vidarabine (ara-A)
___ – this the drug of choice for most situations at present. It is available in a number of formulations
Acyclovir
-I.V. (HSV infection in normal and immunocompromised patients)
* Oral (treatment and long term suppression of mucocutaneous herpes and
prophylaxis of HSV in immunocompromised patients)
* Cream (HSV infection of the skin and mucous membranes)
* Ophthalmic ointment
___ and ___ – oral only, more expensive than acyclovir.
Famciclovir and valacyclovir
___—causing Chicken Pox (Bulutong)-1° infection
* ___—Shingles-2° infection
* Classic disease of childhood with the highest prevalence occurring in
the 4-10 years old age group
* Highly communicable-attack rate of 90% in close contacts
* MOT: Respiratory droplet, Direct contact with lesion.
* Gain entry via the respiratory tract and spreads to the lymphoid
system
* Incubation period: 14 days
* Following the primary infection, the virus remains latent in the
sensory ganglia
Varicella-Zoster Virus
- Varicella
- Zoster
Primary infection
* Incubation period: ___
* Presents fever, lymphadenopathy. a widespread vesicular rash.
* The features are so characteristic that a diagnosis can usually be made on clinical grounds alone.
* Complications are rare but occurs more frequently and with greater
severity in adults and immuno compromised patients.
* Most common complication is secondary bacterial infection of the vesicles.
* Severe complications which may be life threatening include ____, ___ and ___
VARICELLA
- 14-21 days
- viral pneumonia, encephalitis, and hemorrhagic chickenpox
mainly affect a single area of the skin.
* It may occur at any age but the vast majority of patients are more than 50 years of age.
* The latent virus reactivates in a sensory ganglion and tracks down the sensory nerve to the appropriate segment.
* eruption of vesicles in the skin often accompanied by intensive pain which may last for months
_____
* Complications include
1
2
3
HERPES ZOSTER (Shingles)
- (postherpetic neuralgia)
- Ophthalmic zoster
* Generalized zoster
* Ramsay Hunt Syndrome
Varicella-Zoster Virus TREATMENT
1
2
3
- Self-limiting
- Acyclovir
- For Herpes zoster: Famciclovir and Valacyclovir
PREVENTION of Varicella-Zoster Virus
* Chicken pox: ____
* Zoster: __
* Prophylaxis: ____
- Live attenuated vaccine (2 doses)-Varivax®, ProQuad®
- Zostavax, Shingrix (for adults > 50 y.o)
- Passive immunization of Varicella-zoster immunoglobulin (VZIg)
____
* MOT: saliva and sexual contact, hence the name “kissing disease”
* Common in younger children and sexually active adolescents
* Site of latency: __
* infected B-cells are transformed so that they become capable of
continuous growth in vitro
* Associated with various infections
Epstein-Barr Virus (EBV)
- Human herpesvirus 4
- memory B-cells
Epstein-Barr Virus
CLINICAL MANIFESTATIONS
- Infectious Mononucleosis
- Burkitt’s lymphoma
- Nasopharyngeal carcinoma
- Lymphoproliferative disease and lymphoma in the immuno suppressed.
- X-linked lymphoproliferative syndrome
- Chronic infectious mononucleosis
- Oral leukoplakia in AIDS patients
- Chronic interstitial pneumonitis in AIDS patients
“mono”
* Occurs in adolescents and
young adults
* Symptoms: Fatigue, fever,
sore throat, swollen lymph
nodes and splenomegaly
* Treatment: Self-limiting, most
cases resolve on their own
Infectious Mononucleosis
Epstein-Barr Virus (EBV) Hematologic approach
- Absolute lymphocytosis—30% Atypical lymphocytes/Downy Cells
LABORATORY DIAGNOSIS
A Hematologic approach
B Immunologic approach
1 Specific Antibody Test
2 Non-specific Antibody Test
C EBV DNA molecular assays using whole blood
Specific Antibody Test
- EBV Virus Capsid Antigen (VCA) Antibody (Current or past infection)
- EBV Nuclear Antigen (EBNA) Antibody (Past infection)
- EBV Early Antigen (EA) antibody (acute infection especially in
immunosuppressed)
Non-specific Antibody Test
_____- positive only for 2-3 weeks after exposure
Heterophile Antibody Test/ Monospot test (early diagnosis of IM)-
TREATMENT AND PREVENTION
* No antiviral drug
* Self-limiting for 2-3 weeks
* No vaccine
* Avoid sharing personal items like utensils, drinking glasses etc.
Epstein-Barr Virus (EBV)
- Has the largest genome of the human herpesvirus
- Replicates only in human cells
>Fibroblasts, epithelial cells, granulocytes, macrophages and others - Establish latency in ___,___
- Acquired from blood, tissue and body secretions
- MOT: depends on the time, development and population
Cytomegalovirus
- T-cells, macrophages
Cytomegalovirus Early Life
1 During pregnancy (transplacental)
2 During birth (passage to birth canal)
3 After birth (breastfeeding)
Cytomegalovirus Childhood
- Saliva (kissing)
Cytomegalovirus Adult
- Sexual transmission
- Blood transfusion
- Organ transplantation
- Incubation period: 3-6 weeks
- Causes lifelong infection
- May cause asymptomatic shedding
Cytomegalovirus
Cytomegalovirus
Symptoms vary:
A
B
C
D
A. Immunocompetent persons-mild or asymptomatic
B. Immunocompromised patients
* HIV/AIDS: retinitis, colitis, and encephalitis
* Transplant recipient: severe/fatal disease
C. Congenital and perinatal
* Cytomegalic inclusion disease, fetal death
D. Neonates
* Microcephaly, seizure, deafness, mental retardation, jaundice,
purpura, hepatitis
Cytomegalovirus LABORATORY DIAGNOSIS
1
2
3
4
5
- NAAT (PCR, RT-PCR)-blood, urine, saliva, CSF
- Serological assays (CMV IgM, IgG, pp65 antigen)
- Viral culture
- Direct enzyme-linked fluorescent antibody (DEAFF) test
- Direct microscopic examination of lung, liver and kidney biopsy (Owl’s
eye inclusion body)
Cytomegalovirus TREATMENT AND PREVENTION
1
2
3
4
* Prevention is indicated only in high risk cases.
* Screening of blood and organ donors and administration of CMV
immunoglobulins have been employed in prevention.
* No vaccine is available
- Ganciclovir-retinitis and pneumonia
- Valganciclovir
- Foscarnet
- Cidofovir
Are ubiquitous and are Found worldwide
- They are transmitted mainly through contact with saliva and through breast feeding
- infection are acquired rapidly after the age of 4 months when the effect of maternal antibody wears off
- remains latent in the body after primary infection and reactivates from time to time
HHV-6 and HHV-7
Roseola Infantum-fever and rash in
babies
HHV-6
Originally isolated from cells of ____ as well as some lesser known malignancies such as __ AND ____
* MOT: sharing utensils, kissing or close
contact with infected individual, blood
transfusion, organ transplantation, needle
sharing, sexual transmission
HHV-8
- Kaposi’s sarcoma (KS)
- Castleman’s disease and primary effusion lymphomas
