Volume 8 Supplement 1
Cellular tropism exhibited by human T lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2)
© Kannian et al; licensee BioMed Central Ltd. 2011
Published: 6 June 2011
HTLV-1 predominantly transforms CD4+T cells in vitro and induces leukemia and neurological disease in vivo, whereas HTLV-2 shows a preference for CD8+T cell transformation in vitro with limited in vivo pathology. To better understand cellular tropism of HTLV-1 and HTLV-2 early after in vivo infection we determined proviral load and gene expression kinetics of these viruses in purified CD4+ and CD8+T cells from newly infected rabbits.
Materials and methods
New Zealand White rabbits (four/group) were inoculated intravenously with HTLV-1 (Ach), HTLV-2 (pH6neo), and control irradiated producer cells. Blood was collected pre- (week 0) and post-inoculation (weeks 1,2,4,6,8,&12) for detecting antibody responses using line blot assay, and proviral load and viral gene expression in purified CD4+ and CD8+ T cells using real-time PCR.
HTLV-1 and HTLV-2 infected rabbits seroconverted and had detectable proviral loads in both CD4+ and CD8+T cells by 1 wk post infection. HTLV-1 showed slightly higher CD4+T cell proviral loads early, but overtime the virus was detected at higher levels in CD8+T cells. In general HTLV-2 proviral loads were lower than HTLV-1 and throughout the experimental time course the predominant infected cell was the CD8+T cell. HTLV-1 gene expression levels (gag/pol, tax/rex, and hbz) peaked early in CD4+T cells, but overall expression levels over time were higher in CD8+T cells. HTLV-2 gene expression was detected in both CD4+ and CD8+T cells, but was consistently higher in CD8+T cells throughout the study. Viral determinants of tropism with emphasis on Env will also be discussed.
In the infected rabbit, HTLV-1 shows an early preference for CD4+T cells, but over the12 wk study the majority of cells harboring and expressing the virus are CD8+T cells. In contrast, in this early stage of infection, HTLV-2 reveals a preference for CD8+T cells. We speculate that this differential tropism between HTLV-1 and HTLV-2 contributes to the distinct pathobiology of these two related viruses.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.