Enterovirus

Question 1

EV classification and structure

Answer 1

Family: Picornavirus

Now divided into 5 genuses A-E based on homologous in VP1 capsid protein - same serotype diverge by <25%. (Above serotypes included into these 4 different species)

A - Coxsackie A7&A16, EV A71
B- Coxsackie A9, Echoviruses
C- Polio 1-3,
D- EV D68,
E - Rhinoviruses

NON enveloped linear (+)ssRNA
Icosahedral capsid from 4 proteins VP1-VP4 (same as parecho).

Baltimore - IV

Question 2

Enteroviruses receptors

Answer 2

Poliovirus 1-3 - PVR
EV71 - P-selectin gp ligand-1
Coxsackie A - SCARB2
Coxsackie B - CAR
Echoviruses - VLA2 & CD55

Question 3

Important Enteroviruses

Answer 3

1. Coxsackie A16 - HFMD
2. Coxsackie A6 - atypical HFMD
3. EV D68 - Clusters of Resp infections & AFP (similar structure to rhinoviruses and hence the RTI predominance)
4. EV A71 - epidemic paralysis, CNS infection, HFMD
5. PeV A3 - CNS infections

Question 4

EV/PeV replication sites

Answer 4

1. Initial infection using receptors
2. Initial replication in pharynx & terminal ileum with minor viraemia
3. Spread haematogenously to lymphoid tissue
4. Subsequent replication here with major viraemia
5. Spread to target tissue - heart, CNS, Skin

PCR - throat swab/rectal swab —> Blood —> CSF

Question 5

EV incubation & infectivity

Answer 5

3-5 days

Shed from resp tract for 1-3 weeks and stool 3-8 weeks - infectious during these times

Question 6

EV clinical syndromes

Answer 6

1. HFMD- EV A71
2. Atypical HFMD - Coxsackie A6 - vesiculobullous lesions and more widely distributed
3. Herpangina - group A coxsackie
4. AFP - EV A71, EV D68, Polioviruses
5. Meningitis & encephalitis - EV B (B coxsackies & echos)
6. Acute haemorrhagic conjunctivitis- coxsackie A24
7. Pleurodynia - Bornholm syndrome
8. Myopericarditis
9. URI, LRTI

Question 7

EV in pregnancy risk

Answer 7

No generally associated with severe outcomes
Highest risk when infected near term with substantial risk of vertical transmission

Question 8

EV/PeV diagnostics

Answer 8

RT-PCR - Target: 5′UTR - primers derived from the highly conserved 5’ non coding region (NCR)/Untranslated region (UTR) meaning cannot identify serogroups. Also cannot distinguish rhino due to homology in NCR.

Ref lab cell culture for typing or sequencing. VP1 - A minimum of 350nt long VP1 sequence is required for surveillance by reference laboratories. The complete VP1 sequence (∼900nt) is necessary when assigning new EV types.

WGS also used for typing.

Culture: 2-6 days to develops the Enterovirus cytopathic effect. Indirect IF with a broadly reactive mAb used to confirm. NOT RECOMMENDED ANYMORE.

Serology with 4 fold titre increase - no widely used.

Question 9

EV/PeV therapeutics

Answer 9

No FDA approved antivirals.
1. Pleconaril - capsid inhibitor
2. Pocapavir - capsid inhibitor
3. Remdesivir

IVIG in life threatening infections

Question 10

EV vaccine

Answer 10

Three inactivated EV A71 vaccines available in China

Question 11

HFMD

Answer 11

EV A71 & Coxsackie A16

Virus ingested >replication in sub mucosal lymphoid tissues >minor viraemia with dissemination through blood > secondary replication in CNS, heart, liver, skin > major viraemia

Incubation - 3 to 5 days
Infectious for approx 7 days

Atypical HFMD - coxsackie A6 - more widespread & vesiculobullous

Question 12

Aciclovir in EV

Answer 12

NO

Genome of EVs do not encode for thymidine kinase the enzyme necessary for aciclovir activity

Question 13

Acute flaccid paralysis

Answer 13

EV D68, A71, flaviviruses, adenoviruses, and Polio

Anterior horn cell death which is virally mediated

Clinically - preceding RTI followed by limb paresis

CSF PCR, Spinal MR, throat swab for PCR,

Treatment: experimental IVIG