HHV6

Question 1

What types of HHV6 are there?

Answer 1

HHV6A - no diseaes attributed to this

HHV6B - roseola. Most people infected within first 2 years of life

following infection, latency established in CD4 T cells, monocyte, neuronal cells, fibroblasts

Question 2

What is unique about HHV6 compared to other herpes viruses?

Answer 2

HHV6 can be chromosomally integrated in about 1% of patients

Termed CIHHV-6

Question 3

How to diagnose CIHHV-6?

Answer 3

HHV-6 DNA detected in blood usually indicates virus replication.

However, in individuals with CIHHV-6, viral DNA in latent form originating from human chromosomal DNA is persistently detected at high levels in whole blood as well as in “cell free” samples such as serum and cerebrospinal fluid (CSF), since the latter contain cellular DNA released from damaged cells during sample preparation.

Although HHV-6B encephalitis is an accepted albeit rare complication of primary HHV-6B infection in young children, HHV-6 DNA in the CSF of older immunocompetent children and adults is most likely due to latent virus originating from CIHHV-6 rather than central nervous system (CNS) infection

Send whole blood and serum for HHV6 PCR.
Whole blood should have extremely high levels of HHV6 DNA
Serum blood should have 100x lower levels of HHV6 DNA

HHV6 is also present in hair follicles and nails in persons with CIHHV6. Can use FISH to confirm integration into human chromosome

If think it is acquired during transplantation, test pre-transplant bloods

Question 4

What clinical picture is HHV6-B associated with?

Answer 4

HHV6-B

Roseola

Encephalitis - it is the most common cause of infectious encephalitis after allogenic HSCT

Question 5

What is meant by HHV6 reactivation?

Answer 5

Can be:

Endogenous - reactivation of latent virus in cells.
This can include latent virus in cells, or chromosomally integrated HHV6. If child is >2 years old, then assume that they are previously infected

Exogenous - reinfection

Question 6

Patient has known CIHHV6

They present with encephalitis and fever

You detect CIHHV6 DNA

What tests can be done to clarify whether this is endogenous reactivation, or a new infection?

Answer 6

Whole genome sequencing, and compare to identity of integrated virus

If same identity - endogenous reactivation

Question 7

HHV6B encephalitis

What are treatment options?

Answer 7

Reduce immunosuppression if possible

Ganciclovir, foscarnet, cidofovir all inhibit HHV6 in vitro

No studies to prove benefit, but likely worth trialling in high risk bone marrow transplant patients

Monitor response with HHV6 viral loads. Likely need about 3 weeks therapy