Oral Presentation 9th Australasian Virology Society Meeting 2017

Genomics and Pathogenesis of HTLV-1c Prevalent in Australian Remote Indigenous Communities (#50)

David Yurick 1 , Georges Khoury 1 , Ashley Hirons 1 , Hai Pham 2 3 , Ricky Mentha 2 4 , Kim Wilson 5 , Megan Crane 1 , Bridie Clemens 1 , Katherine Kedzierska 1 , Lloyd Einsiedel 2 3 4 , Damian Purcell 1
  1. Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  2. Infectious Disease Unit, Alice Springs Hospital, Alice Springs, NT, AUS
  3. Baker Heart and Diabetes Institute Central Australia, Alice Springs, NT, Australia
  4. Territory Rural Clinical School/Flinders University, Alice Springs, NT, Australia
  5. National Reference Laboratory, St. Vincents Hospital, Melbourne, VIC, Australia

Human T-cell lymphotropic virus type-1 subtype-C (HTLV-1c) infects predominantly CD4+, CD8+ and Ɣδ T-cells and to a lesser extent, B-cells, monocytes, and dendritic cells. HTLV-1c is endemic in remote indigenous Aboriginal communities where prevalence is often greater than 50%1. Peripheral blood mononuclear cell (PBMC) DNA samples were obtained following ethics approval and patient consent in first language. We sequenced the HTLV-1c genomes from 30 patients (Alice Springs Hospital, ASH) and examined the structure of HTLV-1c spliced mRNA. The involvement of HTLV-1c-infected T-cells in clinical pathogenesis was assessed in longitudinal analysis of 84 HTLV-1+ individuals using a digital droplet PCR (ddPCR) assay capable of quantifying the HTLV-1c proviral load (PVL) in total PBMC and in T-cells. The T-cell receptor V-beta locus (TCRβ) gene repertoire of HTLV-1c-infected cells from 22 patients was examined to test for antigen driven T-cell clonal expansion.

Comparison of Cosmopolitan (A) and Austral-Melanesian (C) HTLV-1 clades showed homology greater than 90% across the entire genome. However, the HBZ and p12/p8 coding regions exhibited considerable differences at both the nucleotide (12 and 18%, respectively) and amino acid levels (18 and 25%, respectively). There was no spliced mRNA nor an initiation codon for p12/p8. These features may contribute to the observed inflammatory pathogenesis but with low-rates of T-cell leukaemia which depends on HBZ. Indigenous Australians exhibited a wide PVL per T-cell ranging from 8x102 – 5x106 copies/106 T-cells and suggested expansion in myeloid cells. High PVL strongly associated with chronic inflammatory conditions of the lung, especially bronchiectasis, but the HTLV-1-associated myelopathy observed elsewhere was rare. Most common were skin and blood stream infections suggesting a subtle functional immunodeficiency2. Further studies are needed to examine the functions of HTLV-1c regulatory and accessory genes and to develop vaccines and antiviral drug treatments to combat HTLV-1c transmission.

  1. 1. Einsiedel L et al. MJA 188:568-571, 2008
  2. 2. Einsiedel et al. MJA 2016