Herpes Viruses Flashcards
classify herpes viruses
- Herpes simplex virus, type 1 (HSV1)
- Herpes simplex virus, type 2 (HSV2)
- Varicella-zoster virus (VZV)
- Cytomegalovirus (CMV)
- Epstein-Barr virus (EBV)
- Human herpesvirus 6 (HHV-6)
- Human herpesvirus 7 (HHV-7)
- Human herpesvirus 8 (HHV-8)
define the herpvesviridae
A family of enveloped viruses with a linear, double-stranded DNA structure. Includes herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesviruses 6, 7, and 8.
The capsid of Herpesviridae is helical.
True/False
False
It is icosahedral
envelopes of Herpesviridae confers resistance to the surrounding environment. True/False
False
The envelope is a lipid bilayer covering, which is acquired during virion budding and release from the host cell. Typically less stable in acidic environments and less resistant to dry heat and detergents compared to non-enveloped viruses. Includes some DNA viruses (e.g., herpesvirus, poxvirus, and hepadnavirus) and several RNA viruses (e.g., flavivirus, togavirus, and retrovirus).
The envelope is derived from?
host cell membrane during virion budding
what are the common DNA viruses?
A group of viruses that have genetic material composed of deoxyribonucleic acid (DNA). Includes herpesviruses, poxviruses, hepadnaviruses, adenoviruses, papillomaviruses, polyomaviruses, and parvoviruses.
herpesviridae replicate in the cytoplasm of the cell. True/False
False
DNA viruses replicate in the nucleus of host cells (except Poxviridae).
how acyclovir treats herpesviral infections?
Guanosine analog (nucleoside analog): initially HSV/VZV-coded thymidine kinase monophosphorylates the guanosine analog to an active intermediate, which is then phosphorylated by cellular kinases
The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
Selective action in infected cells only → minimal effect on host cells’ DNA replication
The drugs are only activated in cells infected with HSV or VZV. In addition, the DNA polymerase in human cells has very little affinity for the active form of these drugs.
what is the latency of Herpesviridae?
After primary infection, the HSV remains dormant in the ganglion neurons (e.g., trigeminal, sacral ganglion)
what are the sites of latency of:
1) HSV and VZV
2) EBV and CMV
- HSV 1 & 2 and VZV persist in nerve cells
* EBV & CMV persist in lymphocytes (CMV in monocytes)
what are the triggers of herpesviridae reactivation?
triggered by various factors (e.g., immunodeficiency, stress, trauma) → clinical manifestations
describe the general clinical features of HSV and VZV?
- Infection associated with vesicular lesions of skin/ mucous membranes
- Blister-like lesions, fluid-filled
- Painful
- Ulcerate & become crusted
how HSV cause vesicles?
Cause disease at the site of inoculation (cell lysis)
in what nerve HSV-1 maintains latency?
trigeminal ganglion
how HSV infections are transmitted?
- Transmitted via direct contact with vesicular lesions
- Historically, HSV-1 infected “above the waist” and HSV-2 “below the waist” but epidemiology has changed & either can cause oral or genital disease
- Many acquire HSV in the first few years of life
- 60-90% of adults have had an HSV1 infection
- 15-80% of adults have had an HSV2 infection
- Developing countries have a higher burden of disease
what is Herpetic withlow?
An infection of the dermal and subcutaneous tissue of the fingers caused by HSV-1 (and less commonly HSV-2). Often secondary to primary oral lesions. Manifests with painful, grouped, nonpurulent vesicles and axillary and/or epitrochlear lymphadenopathy proximal to the infection.
what is eczema herpeticum?
An acute skin infection that is most commonly caused by HSV-1 and HSV-2 and primarily occurs in patients with pre-existing skin conditions (classically atopic dermatitis). Patients present with fever, malaise, and disseminated, painful, vesicular lesions. Complications include bacterial superinfection and systemic viral dissemination.
primary infection with HSV is mainly symptomatic. True/False
False.
Majority asymptomatic
what are the clinical features of HSV primary infection?
• Fever, malaise, myalgia, painful local lymphadenopathy
• Vesicular lesions can be widely distributed
– Palate, pharynx, gingivae, buccal mucosa, tongue
• Can also get milder infections i.e. just lips
recurrent oropharyngeal herpes usually involves pharynx. True/False
False
Recurrent oral infection:
–Induced by UV light (sun), fever, trauma, stress
–Usually corners of mouth/ lips
recurrent oropharyngeal infection is more severe. True/False
False
Usually milder than the primary infection
what is the herpes galidatorum?
Herpes gladiatorum is one of the most infectious of herpes-caused diseases and is transmissible by skin-to-skin contact. it is strongly associated with contact sports—outbreaks in sporting clubs being relatively common. Herpes gladiatorum is characterized by a rash with clusters of sometimes painful fluid-filled blisters, often on the neck, chest, face, stomach, and legs. The infection is often accompanied by lymphadenopathy (enlargement of the lymph nodes), fever, sore throat, and headache
herpetic withlow commonly occur due to auto-inoculation after primary oropharyngeal lesion. True/False
True
– May occur due to auto-inoculation
– Can be occupational e.g. in healthcare workers
what is keratitis
inflammation of the cornea. Infectious Staphylococcus, herpes zoster, herpes simplex, and Acanthamoeba. Typically causes severe pain, irritation, redness, watery or purulent secretion, and impaired vision.
define herpes keratitis
- -Keratitis: Inflammation of the cornea
- -Mostly unilateral
- -Complications: Recurrent disease (≈30%)/ permanent scarring/corneal damage /blindness
herpetic keratitis is mostly bilateral. True/False
False
unilateral
herpetic keratitis can lead to scarring and blindness. True/False
True
define Herpetic encephalitis
- -Presents with fever malaise, headache, confusion, behavioral changes, seizures, coma
- -Pathology: hemorrhage, necrosis, edema
- -Typically involves the frontotemporal lobe; often poor outcomes (high mortality)
- -Treatment: IV acyclovir
which obes are commonly involved in herpetic encephalitis
temporal lobes
what are the clinical features of Herpes Simplex encephalitis
1) Focal neurological deficits (primarily affects the medial temporal lobe)
2) Altered sense of smell and loss of vision
- -Aphasia
- -Memory loss
- -Hemiparesis
- -Ataxia
- -Hyperreflexia
3) Seizures (focal or generalized)
4) Altered mental status (e.g., confusion, disorientation, lowered level of consciousness)
5) Behavioral changes (e.g., hypersexuality, hypomania, agitation)
6) Meningeal signs (e.g., nuchal rigidity, photophobia) may occur.
7) Coma
HSE may resemble bacterial meningitis, but the combination of altered mental status, seizures, and focal neurological deficits are more common for HSE!
what are the characteristic features of herpetic encephalitis on imaging
–Magnetic resonance imaging
Most sensitive and specific imaging modality, especially in the early stages
Hyperintense temporal lobe lesions and signal abnormalities (usually in the hippocampus)
–Computed tomography
Often normal during the early stages
A unilateral hypodense zone can be observed in the insular cortex, which may become bitemporal with disease progression.
what are the characteristic features of herpetic encephalitis on lumbar puncture
1) PCR (gold standard): direct, early detection of the pathogen
2) Cells
- -Lymphocytic pleocytosis
- -Erythrocytes may be detected in hemorrhagic encephalitis
3) Other parameters
- -Opening pressure: normal or elevated
- -Protein levels: slightly elevated, ↑ cerebrospinal fluid (CSF)/serum albumin ratio
- -Glucose levels: normal
- -Lactate: varies, mainly normal to slightly elevated
what are the manifestations of HSV 2 infection?
• Genital herpes (sexually-transmitted)
– Historically HSV-2-associated but now more commonly caused by HSV-1
• Can also cause any of the manifestations of HSV-1 infection
• Characteristic vesicular lesions
– Penis in men
– Labia, vagina & or cervix in women (& urethra may be involved)
– Can also get rectal/ oropharyngeal infection with HSV-2
does primary genital herpes cause lymphadenopathy?
Yes
Painful lymphadenopathy in the groin area
define neonatal HSV infection
• Acquired most commonly via the vaginal canal (90%)
–50% chance of neonatal infection if the mother has a primary genital infection at delivery
-However, can be contracted through close contact with someone who has HSV e.g cold sore or herpetic whitlow
• Because of a poor cell-mediated immune response in a neonate, high risk of dissemination and CNS infection
• Consequences include:
-Death
-intellectual disability
-Neurological sequelae
• Most cases occur in babies of mothers who had no signs of HSV infection
transmission of HSV to neonate increases with…
Primary HSV infection in seronegative women has the highest transmission rate (followed by non-primary first-episode infection and, then, recurrent or asymptomatic infection).
how HSV 1 and 2 are diagnosed?
• Laboratory diagnosis not required for minor infections e.g. cold sores
–Diagnosis based on characteristic clinical features
• Serology
–Only HSV IgG serology assay is commonly available
–Can be type-specific e.g HSV -1 IgG or HSV 2 IgG
–The main role of serology is in determining between acute (new) infection and recurrent infection in the maternal setting.
• Genital herpes: PCR on the vesicular fluid used to confirm and to differentiate HSV-1 from HSV-2
• Herpes simplex encephalitis: PCR on cerebrospinal fluid (CSF)
• Neonatal HSV: Surface swabs for culture, CSF & blood for HSV DNA PCR
what are the characteristic findings of Herpes infection with light microscopy?
- -Tzanck smear
- -Multinucleated giant cells (non-specific)
- -Eosinophilic intranuclear Cowdry A inclusion bodies (non-specific)
- -Results available within 1 hour
- -Unable to differentiate between HSV-1 and HSV-2
what is the gold standard for definitive diagnosis of HSV?
Culture results available in 48 hours,
The culture should be taken from a fresh vesicle; cultures of crusted vesicles may yield false-negative results.
how HSV 1 or 2 are treated?
1) First-line: oral acyclovir for mild disease
- -In severe cases or immunocompromised patients → IV acyclovir
- -Topical may be helpful if used early
- -In case of acyclovir-resistant HSV-1: foscarnet
2) Valacyclovir
3) Penciclovir
4) Famciclovir
5) Duration: 7–10 days
acyclovir have effects also on the latent infection. True/False
False
Only replicating cells. The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
what is foscarnet?
A viral DNA/RNA polymerase and HIV reverse transcriptase inhibitor used to treat acyclovir-resistant HSV infections and as a second-line treatment for CMV retinitis in patients who are immunocompromised.
direct inhibition of viral DNA polymerases by binding to the pyrophosphate binding site of the enzyme
Does not require activation by viral kinase vs acyclovir
what’s the difference between valacyclovir and famciclovir vs acyclovir
first 2 are prodrugs
how HSV 1 and 2 need to be prevented?
• No available vaccine
• Simple hygiene measures
• Education regarding infectious stages
–Oral herpes: avoid oral contact with others and sharing objects that have contact with saliva
–Genital herpes: abstain from sexual activity
• Use of condoms
there is a vaccine against HSV 1 or 2. True/False
False
No vaccine
what is the epidemiology of VZV?
≥90% of adults in temperate climates are VZV IgG positive, indicating a previous primary infection
• Most people are infected in early childhood
Highly contagious before & during symptoms
• Rates of infection >90% among susceptible household contacts
Reactivation of the latent virus is known as herpes zoster or shingles
• Occurs in ~30% over a lifetime
• Risk increases with age as cell-mediated immunity wanes
reactivation of latent VZV cause…
shingles (herpes zoster)
what are shingles?
A dermatomal rash with painful blistering caused by the reactivation of the varicella-zoster virus (VZV). Pain can precede the rash. Initial infection with VZV usually occurs early in life, presenting as chickenpox (varicella), and the virus subsequently remains dormant in dorsal root ganglia. Immunosuppressed individuals are at particular risk of VZV reactivation.
why the risk of getting shingles increases with age?
• Risk increases with age as cell-mediated immunity wanes
Immunosuppressed individuals are at particular risk of VZV reactivation.
what are the clinical features of chickenpox?
1)Incubation period: 2 weeks (10–21 days)
Prodromes
2)1–2 days prior to the onset of exanthem
–Presents with constitutional symptoms (e.g., fever, malaise)
–More common with primary infection in adults (less typical in children, in which rash is often the first sign of infection)
3))Exanthem phase: duration: ∼ 6 days
4)Presentation
–Widespread rash starting on the trunk, spreading to the face, scalp, and extremities
–Simultaneous occurrence of various stages of rash: erythematous macules → papules → vesicles filled with a clear fluid on an erythematous base → eruption of vesicles → crusted papules → hypopigmentation of healed lesions
–Severe pruritus
–Fever, headache, and muscle or joint pain
where VZV virus remains for latency?
dorsal root ganglia
what are prodromal symptoms of chickenpox?
constitutional symptoms (e.g., fever, malaise)
what is the pathophysiology of chickenpox?
During the incubation period, the virus attaches to respiratory mucosa, then spreads to regional lymph nodes and via the bloodstream to the liver and spleen (primary viremia).
After the 2-3 week incubation period, there is a secondary viremia; at this stage, the patient is generally unwell and febrile and 1-2 days later the skin lesions develop.
The virus causes skin lesions by lysing epithelial cells (vesicles, then crusts).
