LEC-13 Herpes Viruses Flashcards
What two things do all herpes viruses have in common?
I. Similar size and virion morphology, including envelope
II. They establish latent infection in the host
What viruses are included in the alphaherpesvirus subfamily?
I. HSV-1
II. HSV-2
III. Varicella Zoster virus
IV. Herpes B virus
What viruses are included in the betaherpesvirus subfamily?
I. Cytomegalovirus (CMV)
II. Human herpesvirus type 6 (HHV-6)
III. HHV-7
What viruses are included in the gammaherpesvirus subfamily?
I. EBV
II. HHV-8
What is the primary target cell for HSV-1?
Mucocutaneous epithelium (alpha subfamily)
What is the primary target cell for HSV-2?
Mucocutaneous epithelium (alpha subfamily)
What is the primary target cell for VZV?
Mucocutaneous epithelium (alpha subfamily)
What is the primary target cell for Herpes B?
Mucocutaneous epithelium (alpha subfamily)
What is the primary target cell for CMV?
Monocytes
Lymphocytes
Epithelial cells
(beta subfamily)
What is the primary target cell for HHV-6?
T lymphocytes (beta subfamily)
What is the primary target cell for HHV-7?
T lymphocytes (beta subfamily)
What is the primary target cell for EBV?
B lymphocytes
Epithelial cells
(gamma subfamily)
What is the primary target cell for HHV-8?
Lymphocytes and other cells
gamma subfamily
What is the site of latency for HSV-1?
Neuron (alpha subfamily)
What is the site of latency for HSV-2?
Neuron (alpha subfamily)
What is the site of latency for VZV?
Neuron (alpha subfamily)
What is the site of latency for Herpes B?
Neuron (alpha subfamily)
What is the site of latency for CMV?
Monocytes and lymphocytes (beta subfamily)
What is the site of latency for HHV-6?
T Lymphocytes (beta subfamily)
What is the site of latency for HHV-7?
T Lymphocytes (beta subfamily)
What is the site of latency for EBV?
B Lymphocytes (gamma subfamily)
What is the site of latency for HHV-8?
B Lymphocytes (gamma subfamily)
How is HSV-1 spread?
Close contact
How is HSV-2 spread?
Close contact
How is VZV spread?
Respiratory and close contact
How is Herpes B virus spread?
Monkey bites and saliva
How is CMV spread?
Close contact
Transfusion
Tissue transplants
Congenital.
How is HHV-6 and HHV-7 spread?
Saliva
How is EBV spread?
Saliva (Kissing Disease)
HSV is a(n) (enveloped/naked) virus about ___-___nm in diameter. It contains a (double/single) stranded, (linear/helical) (RNA/DNA) genome.
HSV is an enveloped virus about 150-200nm in diameter. It contains a double stranded, linear DNA genome.
The envelope of HSV is derived from the host’s (cell membrane/inner nuclear membrane).
Inner nuclear membrane
The _______________ and ______________ proteins of HSV are targets for anti-herpesvirus chemotherapy.
DNA polymerase
Thymidine kinase
The immediate-early genes, or (α/β/γ) genes, encode the initial transactivators which initiate transcription of the rest of the viral gene products.
α
The early genes, or (α/β/γ) genes, encode the enzymes involved in DNA replication, such as DNA polymerase and thymidine kinase.
β
The late genes, or (α/β/γ) genes, encode the structural proteins, such as capsid proteins and glycoproteins needed for capsid and envelope assembly.
γ
HSV-1 typically causes lesions of body surfaces (above the waist/below the waist), while HSV-2 usually causes lesions of body surfaces (above the waist/below the waist).
HSV-1 - Above the waist
HSV-2 - Below the waist
The ___________ infection usually initiates with the infection of mucosal body surfaces. This produces a localized response that can be asymptomatic or present with a vesicular skin rash. The virus then spreads to a nerve ending and travels intra-axonally to the nerve cell body, where it establishes other types of infections.
Primary
The ___________ infection is characterized by the absence of infectious virus. This infection typically occurs in sensory neurons of neural ganglia. The viral DNA is maintained in neurons during this time, but does not replicate. This prevents antiviral agents from eliminating the virus during this stage of infection.
Latent
The ___________ infection can be triggered by stressful stimuli including: UV exposure, menstruation, fever, bacterial infection, tooth extraction, or epithelial trauma. This stage of infection involves the renewal of viral replication and production of infectious virus. During this stage, the virus can travel down sensory nerves to re-infect skin where other types of infections have previously occurred. The virus may also move within the CNS to cause encephalitis during this stage.
Reactivated (Lytic)
During primary infection, the first line of defense to HSV is ____________ and ____________.
Interferon and natural killer cells
Following primary infection, ____________ and ____________ limit the spread of the virus.
Macrophages and cytotoxic T cells
(T/F) HSV-1 and HSV-2 are acquired through contaminated respiratory means.
False. HSV-1 and HSV-2 are acquired through close contact with contaminated secretions, body fluids, or vesicular lesions.
(T/F) HSV may be acquired at birth as the newborn passes through the birth canal. Cesarean section is recommended in affected mothers.
True.
(T/F) The seasonal peak of infection for HSV is from April-May.
False. There is no seasonal pattern of infection for HSV.
__________ are the only natural host of HSV.
Humans
(HSV-1/HSV-2) is epidemiologically correlated with cervical carcinoma.
HSV-2
____________ is often the primary infection of HSV-1 and typically occurs in children less than 5 years of age. Incubation periods range from 2-12 days and are followed by fever and the appearance of local oral edema and erythema. Small vesicles develop on the oral and pharyngeal mucosa that rapidly ulcerate. The disease usually runs its course in 10-14 days.
Gingivostomatitis
___________ is the recurrent infection of HSV-1 that causes pain, itching, or a tingling sensation lasting for 6-48 hours prior to the appearance of lesions. Vesicles most often occur on the lip, but may occur anywhere on the face. Lesions progress from the vesicle stage to the ulcer/crust stage within 48 hours. Healing occurs without treatment in 8-10 days.
Herpes labialis (cold sores)
HSV may also result in a condition known as _____________. This condition is characterized by follicular conjunctivitis with regional adenopathy. Photophobia, tearing, and edema of the eyelids may be present. Some patients develop dendrites on the corneal epithelium. Recurrent infections of this condition may manifest as keratitis or blepharitis (inflammation of the eyelid). Stromal scarring can lead to decreased visual acuity and loss of sensation in the cornea. Blindness may result in extreme cases.
Keratoconjunctivitis
______________ is a disease caused by HSV that results in widespread herpetic lesions of the skin. It is often seen in wrestlers as the virus spreads into cuts and abrasions under conditions of close body contact.
Gladiatorum
_______________ refers to herpetic infection of the finger due to being bitten. It is most often an occupational disease seen in dentists, nurses, and others who may be bitten. HSV-1 is more often the cause of this condition than HSV-2.
Herpetic Whitlow
In the US, most genital herpetic lesions are caused by (HSV-1/HSV-2).
HSV-2
Recurrent genital herpes tends to be more severe in (men/women).
Women
(T/F) HSV may cause meningitis, encephalitis, and other neurological diseases. This is quite common.
False. While HSV may cause meningitis, encephalitis, and other neurological diseases, it is quite rare.
Neurological diseases caused by HSV are often preceded by ______-like symptoms.
Flu-like symptoms
_____________ and _____________ are the first presenting signs of a neurological illness caused by HSV, followed by headache, fever, speech disorder, and seizures.
Confusion and behavioral changes
The CSF of patients with a neurological disease caused by HSV shows (increased/decreased) cell counts, (normal/increased) protein levels, and (normal/increased) glucose.
Increased cell counts
Normal protein levels
Normal glucose
(T/F) In suspected cases of HSV encephalitis, an antiviral drug should be started IMMEDIATELY. The longer the treatment is delayed, the poorer the outcome.
True.
Neonatal infections are most often caused by (HSV-1/HSV-2).
HSV-2
The risk of neonatal herpes is higher in women with (primary/recurrent) infections.
Primary
Congenital infections of HSV are recognizable at birth by what signs?
I. Hepatosplenomegaly
II. Microencephaly
III. Signs of CNS involvement
Diagnosis of HSV infections is generally conducted by viral culture. However, in the cases of encephalitis caused by HSV, a(n) ____________ is necessary for diagnosis.
Brain biopsy
Detection of HSV (IgG/IgE/IgD/IgM/IgA) antibodies indicates an acute HSV infection.
IgM
_______________ is the prototype antiviral agent against HSV.
Acyclovir
Why is acyclovir only specific for virally infected cells?
Acyclovir only undergoes its initial phosphorylation to become active by the viral kinase, thymidine kinase.
In what 3 ways does acyclovir exert its effects?
I. Chain terminator of viral DNA synthesis
II. Incorporation into DNA causing errors in replication or RNA transcription
III. Indirect inhibition of the DNA polymerase
Acyclovir serves as a(n) ____________ nucleotide analog.
Guanosine
____________ is often used against acyclovir resistant HSV.
Foscarnet
Antiviral drugs (can/cannot) prevent or eradicate HSV and VZV during latent periods.
Cannot
(T/F) VZV size, structure, envelope, and replication are similar to HSV.
True.
VZV is most often transmitted by (close contact/respiratory routes).
Respiratory routes
_______________ is usually seen in children and presents with a rash, low grade fever, and malaise after a 10-14 day incubation period. The rash, which is the hallmark of the infection, begins on the trunk and face. It consists of maculopapules, vesicles, and scabs in various stages of evolution. The rash spreads quickly and is accompanied by a hike in fever. The lesions initially contain a clear liquid, but they rapidly pustulate and scab.
Varicella (chicken pox)
______________ is the reactivated disease associated with a VZV infection. It is characterized by unilateral vesicular eruption that follows a dermatomal distribution. Thoracic and lumbar dermatomes are more commonly involved, but reactivation from the trigeminal ganglia can involve the face and eyes. The lesions are macropapular, erythematous, and evolve into a vesicular rash. The most significant clinical problem associated with this illness is post-herpetic neuralgia.
Zoster (shingles)
_____________ is an encephalopathy associated with liver dysfunction and cerebral edema.
Reye’s syndrome
Reye’s syndrome is a rare complication of chicken pox in children, but it may also be caused by ingestion of certain drugs. Due to dangers of Reye’s syndrome development, ___________ is contraindicated to control fever during varicella. Acetaminophen should be used instead.
Aspirin
Reye’s syndrome has been linked to ingestion of salicylic acid
(T/F) A vaccine for VZV now exists that confers life-long immunity.
True. The Varicella Oka vaccine
HSV-1 establishes latent infections within the (trigeminal/sacral) ganglia.
Trigeminal
HSV-2 establishes latent infections within the (trigeminal/sacral) ganglia.
Sacral
HSV encephalitis usually affects the ____________ lobes of the brain.
Temporal
Varicella infections are most common in the _________ and _________ seasons.
Winter and spring
A 67 year old man develops a painful vesicular skin rash with dermatomal distribution on the chest. Which of the following is TRUE?
- The lesions will likely progress to the other side of the chest
- He probably got the disease after exposure to a child with chickenpox
- He may transmit the disease to his wife
- An effective antiviral agent is available for treatment
- A killed vaccine can prevent this disease
- is false -> Dermatomal shingles never cross the midline.
- is false -> Shingles is endogenous, you can’t get it from someone else.
- is false -> Can’t give another person shingles. Only chickenpox.
- is true.
- is false -> There is only a live vaccine.
VZV establishes latent infection within the dorsal root of the _________ ganglia and throughout the neuraxis (cervical, thoracic, lumbar, and sacral ganglia).
Trigeminal
(T/F) You may not transmit shingles to another person, but you may cause chickenpox in a child if you are experiencing shingles.
True.
Zoster infections (cross/do not cross) the midline.
Do not cross the midline
Chickenpox and shingles are usually diagnosed based upon ____________ and ____________.
Patient history and clinical symptoms
