Common Viral Pathogens II

Question 1

Herpes simplex type 1 primary infection

Answer 1

1. Asymptomatic: most common
2. Gingivostomatitis: painful mouth vesicles and ulceration of gums, lips and tongue, usually in anterior mouth
3. Occasionally: genital herpes, herpes keratitis (infection of cornea -> dendritic lesions -> scarring and blindness), herpetic whitlow (virus gains entry into skin of finger—OCCUPATIONAL HAZARD—seen when infected mother kisses “owie” on kid).
4. Rare: Encephalitis that occurs through blood-borne spread or neuronal transmission of virus (predilection for temporal lobe), has a 30% mortality rate. HSV-1 causes most cases of childhood and adult encephalitis.

Question 2

Herpes simplex type 1 reactivation

Answer 2

1. Viral shedding with no symptoms is most common
2. Most common symptomatic reactivation is herpes labialis (cold sores).
3. Occasionally: recurrent genital herpes or herpes keratitis
4. Rare: encephalitis

Question 3

Herpes simplex type 2 primary infection

Answer 3

1. Asymptomatic: most common
2. Genital herpes—HSV-2 causes 70% of genital herpes, STI, painful vesicles and ulcers in the genital and perianal region, lesions last 10-14 days, urination can be painful and require catheter
   a. Neonatal herpes: perinatally acquired HSV infection that develops during 1st month of life, primary herpes infection of neonate, transmitted during birth from exposure to maternal secretions with HSV-1 or 2, but since most genital herpes is HSV-2 most neonatal herpes is caused by HSV-2. Finding a vesicle in neonate less than 4 weeks of age is a medical emergency (20-50% mortality rate).
3. Occasionally: gingivostomatitis
4. Rare: encephalitis, herpetic whitlow or herpes keratitis

Question 4

Herpes simplex type 2 reactivation

Answer 4

1. Viral shedding and no symptoms is most common
2. Most common symptomatic reactivation is recurrent genital herpes
3. Occasionally: gingivostomatitis
4. Rare: encephalitis and herpes keratitis

Question 5

Varicella zoster primary infection

Answer 5

1. Chicken pox (“varicella”): highly contagious, childhood disease, transmitted through droplets and aerosolized secretions, symptoms: fever, malaise, headache, cough, rash appearing in “crops” or waves (as successive crops appear, the lesions will be noted to be in various stages of development—vesicle, pustule, crust, scab), rash begins on trunk and spreads to face and limbs. Initial lesion: flat and rose colored, which mature into “dew drop on a rose petal”. Most lesions on trunk and face, then arms and legs.

Question 6

varicella zoster reactivation

Answer 6

1. Following primary infection, the virus remains latent in the cerebral or dorsal root ganglia (areas associated with areas in which the virus was present in the skin). In 10-20% of people, a single reactivation of infections, Shingles “herpes zoster or zoster”, occurs after several decades. Reaction caused by stress, immune suppression. Once reactivated, virus tracks down the sensory nerve to the area of skin that the nerve innervates producing a varicella-form rash (grouped vesicles on an erythematous base) in that dermatome (they do not cross mid-line). Inflammation, necrosis of cells in ganglion and neuropathic pain occurs. Lesions heal in 2 weeks. Shingles is more common in the elderly, reflecting that lowered cell-mediated immunity may play a role. There are fewer exposures to natural chickenpox in community because all children are vaccinated, thus there are no ways to “boost” immunity.
   a. Complication: post-herpetic neuralgia: primarily in elderly, chromic burning, itching or shooting pain, may last weeks to months after rash has healed.
2. VZV is the only Herpesviridae virus that DOES NOT exhibit an asymptomatic viral shedding in normal hosts that experience reactivation

Question 7

EBV primary infection

Answer 7

1. Commonly asymptomatic in children or is a mild, non-specific, febrile illness.
2. Acquired as a teen or young adult, 40-50% of the time EBV causes infectious mononucleosis (the rest of the time it is asymptomatic). Infectious mono symptoms are sore throat with tonsilar enlargement and exudates, fever, lymphadenopathy, fatigue and malaise. Palatal petichiae present in 30-60% of patients. CBC shows 50% lymphocytes, with at least 10% atypical lymphocytes (large, with blue/grey basophilic cytoplasm, cytoplasm indented around RBCs)

Question 8

EBV reactivation

Answer 8

EBV remains dormant or latent in B cells or nasopharyngeal epithelium. During latent infection, virus present in lymphocytes and oropharyngeal epithelial cells takes the form of episomes in the nucleus. Reactivation can take place resulting in intermittent shedding of EBC from saliva. Usually occurs without any symptoms

Question 9

CMV primary infection

Answer 9

1. Usually asymptomatic in people with normal immune systems
2. If symptoms occur they are: 1) mild febrile illness or 2) mononucleosis-like illness with fever, swollen nodes, mild hepatitis.
3. In immunocompromised patient, primary infection can infect most organs causing pneumonia, colitis, hepatitis, encephalitis, retinitis, etc.

Question 10

CMV reactivation

Answer 10

1. Reactivated during which infectious virions appear in the urine and saliva. Reactivation can lead to vertical transmission (mom to baby), but this is more common when mother has primary CMV infection

Question 11

Complications of chickenpox:

Answer 11

primary infection
a.	Secondary infection or cellulitis
b.	Pneumonia
c.	Necrotizing fasciitis
d.	Encephalitis or encephalomyelitis
e.	Hepatitis 
f.	Congenital varicella syndrome
Reactivation 
a.     post-herpetic neuralgia: primarily in elderly, chromic burning, itching or shooting pain, may last weeks to months after rash has healed.

Question 12

herpesvirus virion structure

Answer 12

• dsDNA
• icosahedral capsid
• glycoprotein-rich envelope

Question 13

Herpesvirus subfamilies and sites of latency

Answer 13

• alpha subfamily –> latency in sensory ganglia
• beta subfamily –> latency in monocytes and lymphocytes
• gamma subfamily –> latency in B cells

Question 14

Herpesvirus replication

Answer 14

• Immediate early (IE) genes are expressed prior to protein synthesis (brought in with the virus). IE genes are required for the expression of the early (E) and late (L) genes, which are de novo synthesized. Many IE genes encode transcriptional activators.
• E genes encode proteins involved in DNA replication, such as viral DNA polymerase, thymidine kinase (TK), helicase, etc. (Many drug targets are to these virally-encoded proteins. For example, acyclovir and ganciclovir act on TK, and foscarnet acts on viral DNA polymerase.)
• L genes encode structural proteins, such as capsid and glycoproteins.