Herpesviridae Flashcards
What are the members of the virus family Herpesviridae?
- HHV-1 (herpes simplex virus, type 1 [HSV-1])
- HHV-2 (herpes simplex virus, type 2 [HSV-2])
- HHV-3 (varicella-zoster virus [VZV])
- HHV-4 (Epstein–Barr virus [EBV])
- HHV-5 (cytomegalovirus [CMV])
- HHV-6
- HHV-7
- HHV-8 (Kaposi sarcoma herpesvirus [KSHV])
What are the subfamilies of the family Herpesviridae?
- Alphaherpesvirinae: HHV-1, HHV-2, HHV-3
- Betaherpesvirinae: HHV-5, HHV-6, HHV-7
- Gammaherpesvirinae: HHV-4, HHV-8
What is the general structure of human herpes viruses?
Enveloped viruses with double-stranded DNA genomes
What is the common feature shared by all herpes viruses?
- They establish lifelong persistent latent infection, with periodic reactivation
- The reactivation can be asymptomatic or symptomatic (especially if cellular immunity is suppressed)
Which human herpes viruses belong to the subfamily Alphaherpesvirinae?
- HHV-1 (HSV-1)
- HHV-2 (HSV-2)
- HHV-3 (VZV)
Which herpes viruses are herpes simplex viruses?
- HHV-1 (HSV-1)
- HHV-2 (HSV-2)
To which subfamily do herpes simplex viruses belong?
Alphaherpesvirinae
How are herpes simplex viruses transmitted?
- Direct contact
- Saliva
- Sexual transmission (especially for HSV-2)
- Vertical transmission
What is the clinical manifestation and progression of primary infection with herpes simplex viruses?
The virus infects the skin and mucous membranes, causing lesions. The lesions progress as:
- Macules (small, flat lesions)
- Papules (small, raised lesions)
- Vesicles (small, raised lesions filled with a clear fluid)
- Ulcers (vesicles which have opened)
- Crusting over of the ulcers
These lesions last 1–2 weeks and can be very painful
How do herpes simplex viruses become latent?
- The nucleocapsid (i.e. the virion without the capsule) enters sensory nerve endings
- The virus is transported by retrograde axonal transport to the dorsal root ganglion
- The virus establishes latency in the nucleus
What are the common sites of latency for the herpes simplex viruses?
- HSV-1: trigeminal nerve
- HSV-2: sacral ganglia
How do latent herpes simplex viruses escape immune detection?
There is no active replication of the virus, so no virus proteins are produced for detection
What can trigger reactivation of herpes simplex viruses?
- Stress
- Fever
- Suppressed cellular immunity
How are herpes simplex viruses reactivated?
The virus moves by anterograde axonal transport to the sensory nerve endings and establishes infection in the skin and mucous membranes
What is the clinical manifestation of reactivated herpes simplex virus?
- Mostly asymptomatic (up to 90% for HSV-1)
- The patients are still infectious
What are the diseases caused by herpes simplex virus?
- Gingivostomatitis (inflammation of the gums and oral mucosa)
- Pharyngitis and tonsilitis
- Conjunctivitis
- Keratitis
- Cold sores (i.e. fever blisters, herpes labialis)
- Cutaneous herpes
- Herpetic whitlow (in the fingers)
- Eczema herpeticum (more severe whitlow in those with allergic dermatitis)
- Genital herpes
- Herpes encephalitis
- Herpes meningitis
- Neonatal herpes
- Disseminated severe disease (usually in immunosuppressed patients, e.g. AIDS patients)
Which disease caused by HSV-1/HSV-2 is most associated with occupational exposure, especially in dentists?
Herpetic whitlow
How severe is neonatal herpes?
Very severe, with a mortality rate of around 60%
How is herpes simplex virus diagnosed?
- Clinical presentation (although the lesions don’t point definitively to HSV)
- PCR
- Serology: IgM for primary infection, IgG for past infection
- Nuclear inclusions in cells (using a Tzanck smear)
How is herpes simplex virus treated?
Antiviral nucleoside analogs: acyclovir, valacyclovir, vidarabine. These do not affect the latent virus
Is there a vaccine for herpes simplex virus?
No
What is the epidemiology of herpes simplex viruses?
- More than 90% of young adults have already been infected by HSV-1
- HSV-2 is much less prevalent due to its sexual spread
How is varicella-zoster virus transmitted?
- Direct contact
- Aerosols (droplet nuclei)
What is the clinical manifestation and progression of primary infection with VZV?
- The virus accesses the upper respiratory tract and replicates there
- It spreads into the blood (primary viremia), followed by replication in the liver and spleen
- It spreads in the blood again (secondary viremia) to the skin, giving rise to chickenpox (varicella)
- The chickenpox rash is highly pruritic (itchy)
In VZV infections, what is the difference between primary and secondary viremia?
- Primary viremia: the first spread of the virus into the blood, occurring after replication in the upper respiratory tract
- Secondary: the second spread of the virus into the blood, following replication in the liver and spleen
What is the clinical manifestation and progression of secondary infection with VZV?
- The virus causes lesions (called shingles or zoster) in one or a few skin segments innervated by the dorsal root ganglion it was latent in (along a dermatome)
- The lesions are extremely painful
- Pain may continue for months after the lesions disappear (post-herpetic neuralgia)
A man who has never been exposed to VZV is infected by a colleague with shingles (zoster). Which disease, varicella or zoster, will he develop?
Varicella (as it will be primary infection)
What are potential complications of chickenpox?
- Pneumonia and meningitis
- Mortality is very low (1 per hundred thousand; slightly higher in adults)
- Neonatal infection is severe with a mortality rate of 30%
How is VZV diagnosed?
- Clinical presentation
- PCR
- Serology: IgM for pirmary infection, IgG for past infection
- Nuclear inclusions in cells (using a Tzanck smear)
Which virus is referred to as varicella-zoster virus (VZV)?
HHV-3
To which subfamily does varicella-zoster virus belong?
Alphaherpesvirinae
How is varicella treated?
Symptomatic treatment
How is zoster (and resultant post-herpetic neuralgia) treated?
- Antivirals acyclovir, valacyclovir, and famciclovir can reduce the length and severity of infection
- For neuralgia: tricyclic antidepressants, gabapentin (an anticonvulsant), pregabalin (an anticonvulsant), opioids, tramadol (an opioid and SNRI)
Is there a vaccine for VZV?
- Live attenuated virus to prevent chickenpox
- Therapeutic vaccines to reduce occurrence of zoster (both recombinant subunit and live attenuated vaccines)
What is the epidemiology of VZV?
- Childhood infection is extremely common in countries where vaccination is not offered (due to the cost of the vaccine)
- Incidence of zoster increases with age
Which virus is referred to as Epstein–Barr virus?
HHV-4
To which subfamily does Epstein–Barr virus belong?
Gammaherpesvirinae
How is EBV transmitted?
Saliva (so, primary infection is called “kissing disease”)
Primary infection with which virus is referred to as “kissing disease?”
EBV
What is the tropism of EBV?
- B cells
- Epithelial cells
What is the site of latency of EBV?
B cells
Which receptor does EBV use to enter cells?
CD21 (complement receptor 2)
What are the clinical manifestations of primary infection with EBV?
- Most infections are asymptomatic, especially in children
- In adults, infectious mononucleosis may occur
- The classical triad of infectious mononucleosis is fever, pharyngitis, and cervical lymphadenopathy
- Adults may also develop fatigue, headache, and splenomegaly
Which cancers are linked with EBV?
- Burkitt lymphoma
- Nasopharyngeal carcinoma
- Gastric carcinoma
- Hodgkin and non-Hodgkin lymphomas
Which disease linked to EBV infection is prominent in AIDS patients?
Oral hairy leukoplakia: a benign wart-like growth on the tongue
How is EBV diagnosed?
- Clinical presentation
- Blood film showing atypical lymphocytes: these are large T cells reacting to the infected B cells
- PCR
- Serology: IgM to viral capsid antigen (VCA) in primary infection; IgG to EBV nuclear antigen (EBNA) for past infection
How is EBV treated?
Supportive treatment
Is there a vaccine for EBV?
No
What is the epidemiology of EBV?
- More than 90% of young adults have already been infected
- In developing countries, infection occurs in early childhood
- In developed countries, infection occurs in mid-/late-adolescence with the onset of sexual activity and kissing
What virus is referred to as cytomegalovirus?
HHV-5
To which subfamily does cytomegalovirus belong?
Betaherpesvirinae
How is CMV transmitted?
- Saliva
- Direct contact
- Vertical: CMV is the most common congenital infection
Infection with which virus is the most common congenital infection?
CMV
What is the clinical manifestation of primary infection with CMV?
- Most infections are asymptomatic, espeically in children
- In adults, mononucleosis-like syndrome may occur (with the same symptoms as mononucleosis)
What is the result of congenital infection with CMV?
- Deafness
- Blindness
- Mental retardation
What diseases can be caused by CMV in immunosuprressed patients?
- Pneumonia
- Gastroenteritis
- Retinitis
How is CMV diagnosed?
- Clinical presentation
- Blood film showing atypical lymphocytes
- PCR
- Serology: IgM in primary infection, IgG for past infection
How is CMV treated?
- Normal primary infection: supportive therapy
- In immunocompromised patients and congenital infection: ganciclovir
Is there a vaccine for CMV?
No
What is the epidemiology of CMV?
More than 90% of young adults have already been infected
What viruses are referred to as roseola viruses?
HHV-6 and HHV-7
To which subfamily do the roseola viruses belong?
Betaherpesvirinae
How are HHV-6 and HHV-7 transmitted?
Saliva
What are the clinical manifestations of roseola virus infections?
- Infection is usually acquired in the first year of life
- The disease (roseola infantum, aka exanthema subitum, sixth disease) is characterized by high fever and skin rash
How are roseola viruses diagnosed?
- Clinical presentation
- PCR
How are roseola viruses treated?
Supportive therapy, especially using antipyretics to lower the fever
Are there vaccines for HHV-6 and HHV-7?
No
What is the epidemiology of roseola viruses?
More than 90% of children have already been infected
What virus is referred to as Kaposi sarcoma herpesvirus?
HHV-8
To which subfamily does Kaposi sarcoma herpesvirus belong?
Gammaherpesvirinae
How is KSHV transmitted?
- Saliva
- Sexual transmission (especially among homosexual males)
- Vertical transmission (especially in Africa)
What are the clinical manifestations of infection of KSHV?
- Primary infection is asymptomatic in immunocompetent people
- In AIDS patients or the elderly, Kaposi sarcoma (cancer of the blood and lymph vessels) can occur. This appears on the skin or mucous membranes
How is KSHV diagnosed?
- Histopathology
- PCR
Is there a vaccine for KSHV?
No
What is the epidemiology of KSHV?
- Low prevalence in the general population
- Prevalence is higher among male homosexuals
