HTLV

Question 1

HTLV structure & classification

Answer 1

Family: Retroviridae
Genus: Deltaretrovirus

Diploid genome 2x (+)ssRNA

Baltimore: VI

Genome: 5’LTR-gag-pol-env-pX-LTR3’

Question 2

HTLV receptor & tropism

Answer 2

Receptor- Virion entry happens most efficiently by cell-to-cell contact via a viral synapse but GLUT-1 & CCR4 used by cells free virions.

Tropism - CD4 T cells

Question 3

HTLV life cycle

Answer 3

1. Cell entry by cell-to-cell viral synapse OR GLUT-1/CCR4 by cell free virons.
2. RNA reverse transcription to DNA.
3. Integration into host genome.
4. Viral replication - mitotic cell division or by integrate provirus re-expressing.

HTLV had LOW LEVEL viraemia and cell infection rates compared to HIV. There are also no cytopathological effects on the T cells.

Question 4

HTLV & breast milk

Answer 4

15% risk of vertical transmission with breastfeeding > 6 months

Question 5

HTLV needlestick risk

Answer 5

Very low - reassure

Australia - 53 HCWs with needlestick from HTLV-1 positive index - 0 transmission events

Question 6

HTLV clinical syndromes

Answer 6

1. Majority asymptomatic
2. Adult T cell Lymphoma (ATL)
3. HTLV-1 associated myelopathy (HAM) - previously called TSP

Question 7

HTLV ATL risk, timeline, pathology

Answer 7

Risk- 2 to 5%
Timeline - 20-30 years post infection

Mechanism of oncogenesis: Tax & HBX oncoprotein induces cellular proliferation and cellular survival, impairs DNA damage repair mechanisms.

Clonal proliferation of CD4 T cells containing integrated HTLV.

Skin nodules, lyric bone lesions, pulmonary infiltration, hypercalcaemia, CNS lymphoma (10%). HSM, Lymphadenopathy.

Smouldering ATL- <5% CD4 cells involved and more indolent.

Treatment: Chemo as for NHL - CHOP

Question 8

HTLV HAM risk, timeline, pathology

Answer 8

Risk- 2%
Timeline - median 3.3 years

Slow onset spasticity of legs, hyper reflexes, clonus, extensors, incontinence, parasthesia. NO UPPER LIMB/COGNITION INVOLVEMENT.

Therapeutics: Pulsed methyl pred plus low dose maintanence steroids + methotrexate/MMF. But NO RCTs.

Question 9

Mogamulizumab

Answer 9

Anti-CCR4 mab used in Japan for ATL & HAM - unclear efficacy.

Question 10

HTLV diagnostics

Answer 10

WINDOW PERIOD: 65 days

1. ELISA screening - can’t tell HTLV 1/2 apart.
2. Western Blot confirmation - gag & env antibodies. WB also differentiates HTLV1 vs 2.
3. Proviral DNA RT-PCR on blood and CSF - 4 times higher in CSF in HAM

CSF - leukocytosis, elevated protein, pro viral DNA

Question 11

HTLV therapeutics

Answer 11

Supportive if clinical syndrome

Antivirals NOT indicated.

INSTIs & NRTIs show in vitro efficacy

Zidovudine & lamivudine have shown variable effect in various trials.

HAM - Methotrexate + steroid to slow progression.

Question 12

HTLV PEP

Answer 12

Off label - Truvada + raltegravir

despite the lack of HTLV-1 PEP or PrEP trials, licensed HIV-1 PrEP drugs are prescribed off-licence to prevent the transmission in HTLV-1 to organ donors and during occupational exposure10 and have been repurposed to prevent mother-to-child HTLV-1 transmission

some specialists recommend that individuals who have sustained a significant occupational exposure to HTLV-1 should receive post exposure prophylaxis with raltegravir, zidovudine and lamivudine for 6 weeks