Lecture 80 - Herpes Simplex Viruses: HSV 1, HSV 2

Question 1

Structure of Herpes Simplex Viruses

Answer 1

Icosahedral - 162 Capsomeres

• double stranded, Linear DNA
• Nucleocapsid surrounded by Tegument
• Enveloped

Question 2

What proteins are present in the tegument?

what is the important glycoprotein of the lipid envelope?

Answer 2

Tegument:
Vp16 – trans-activator protein required for initial amplification
VHS – Inhibitor of the cell macromolecular metabolism and protein synthesis

Lipid Envelope:
- Glycoprotein D – important for binding and fusion to host

Question 3

Describe the HSV Life-Cycle

Answer 3

Attachment – cell surface receptor (Viz, Nectin 1); Viral glycoprotien D

Fusion – envelopes fuse

DNA is deposited to the nucleus

mRNA exits the nucleus ; proteins move back in the nucleus

Assembly occurs in the nucleus

Envelope acquired from budding out of the nuclear membrane

Virus eventually lysis and kills the cell

Question 4

HSV DNA Replication

Answer 4

Linear DNA enters the nucleus and Circularizes

First wave of Replication = “Rolling Circle”

Later waves of replication = “strand invasion” — homologous recombination between nascent and original strands leading to irregular branched apperaance

This complex structure is cleaved by viral nucleases; leading to formation of a concatamer

Concatamer is cleaved upon packaging into capsid

Question 5

HSV 1 and 2

• in general – what are the clinical manifestations
• describe some epidemiology

Answer 5

HSV 1 - facial herpes, some genital sores, can lead to encephalitis (most commonly reported viral CNS infection)

HSV 2 – Genital herpes; can lead to meningitis

Epi:
80% of adults are infected with HSV
40 to 60 millon cases of Genital herpes in the US
50 to 100 million cases of facial herpes infections
Women are 45% more likely to be infected with HSV 2

Question 6

HSV Pathogenesis – Primary and Recurrent infections

Answer 6

primary infection: 80+% asymptomatic; 20% Symptomatic

• Local symptoms: lesions, pain, itching, dysuria
• Systemic Symptoms: fever, HA
• Lesions are vesicular, wet ulcerated, crusting
• Healing – days 15-25 after onset of lesions

Recurrent Infection:

• Preceded by prodromal symptoms; tingling sensation
• Lesions and shedding of shorter duration
• Local symptoms
• No systemic Symptoms
• Healing occurs days - 10-15 after symptom onset

Question 7

Describe the Skin lesions of HSV infection

Answer 7

Vesicular lesions, fluid filled on severely erythematous space

Can appear pustular

Question 8

Describe an unusual presentation of HSV infection

Answer 8

Unusual to appear as “crater”

Tumoral Presentation — hypertrophic lesions; more commonly in the immuno compromised

Question 9

• HSV Encephalitis (HSE)
What is the gold standard for Dx ?

Answer 9

HSE – HSV 1
Most common viral CNS infection
Temporal and Frontal Lobes
Dx – PCR of HSV DNA in CSF

HSV Meningitis – HSV 2

Question 10

Neonatal HSV

• how is it transmitted?
• Major risk?

Answer 10

Transmission – acquired upon passage through birth canal

Major risk is primary infection occurring near to term

Transplacental transmission is rare

can lead to CSN HSV – treat with aciclovir

Question 11

Describe the process of HSV latency

what are the three key things to remember

Answer 11

-Penetration into the skin/mucosa
- Local Replicaiton and entry of the virus into a cutaenous neurons
- Migration of uncoated nucleocapsids up the axon to the Ganglia (DRG vs Trigeminal)
- Genome enters the nucleus – Circularizes – but DOES NOT INTEGRATE
- Exists as Episome
- expresses no transcripts except LAT (latency associated transcript)
-
3 things: Episome, circular, LAT

Question 12

what neurons do HSV 1 and HSV 2 prefer?

Answer 12

HSV 1 - A5+ neurons

HSV 2 - KH10 (CDNF+) Neurons

Question 13

Describe some means of maintenance of latnecy and Reactivation

Answer 13

Histone methylation

Question 14

Diagnosis standards

Answer 14

Tzanck Smear – smear of open skin vesicle – looking for specific multinucleated giant cells. Insensitive

Shell Vial/ Ag Detection

PCR – gold standard for HSE

Serology – takes 3 to 7 days (????) after infection; once person is infected, have antibodies for life, but doesn’t tell you anythin about the initial infection. Also don’t prevent recurrence but do ameliorate severity

Question 15

Role of Adaptive immunity

Role of Innate Immunity

Answer 15

Adaptive – IgM and IgG – persist for life. Don’t prevent recurrnence but do play role in regulating severity

Innate – NK, DC, INF gamma, TNF alpha
play a role in containment
imparied TLR associated with HSV 1 replication in the CNS

Question 16

Treatment

Answer 16

aciclovir