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. 2011 Jan;2(1):89-93.
doi: 10.3892/etm.2010.179. Epub 2010 Dec 2.

Route of primary HTLV-1 infection regulates HTLV-1 distribution in reservoir organs of infected mice

Masakazu Tanaka  1 , Takayuki Nitta, Binlian Sun, Jun-Ichi Fujisawa, Masanao Miwa
Affiliations

Route of primary HTLV-1 infection regulates HTLV-1 distribution in reservoir organs of infected mice

Masakazu Tanaka et al. Exp Ther Med. 2011 Jan.

Abstract

Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia and HTLV-1-associated myelo-pathy/tropical spastic paraparesis. HTLV-1 is mainly transmitted through blood transfusion and breastfeeding, but viral proliferation in the body in vivo shortly after transmission is not well understood. To investigate whether the route of infection influences the early stages of viral proliferation, we inoculated BALB/c mice with MT-2 cells, an HTLV-1-producing human T-cell line, via different routes, and evaluated the proviral load and humoral immune responses. One month after infection, the provirus was detected in most organs of the mice infected intraperitoneally, and substantial proviral loads were detected in the peripheral blood and secondary lymphoid organs. In contrast, the mice infected intravenously and orally showed low proviral loads, and the provirus distribution was limited to the spinal cord among the intravenously inoculated mice and to the liver among the perorally inoculated mice. Mice infected intraperitoneally also exhibited higher interleukin-2 production than the mice infected intravenously or orally, or than the uninfected control mice, while anti-HTLV-1 antibody titers were comparable between the mice infected intraperitoneally and intravenously. These results demonstrate that the route of primary HTLV-1 infection influences the establishment of HTLV-1-infected cell proliferation and the cell reservoir in mice.

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Figures

Figure 1.
Figure 1.
Antibody response against HTLV-1 and Interleukin-2 (IL-2) production in the serum. BALB/c mice were inoculated with 106 MT-2 cells intraperitoneally (IP), intravenously (IV) or perorally (PO) and sacrificed 1 month after infection. Control mice were inoculated with phosphate-buffered saline. (A) Antibody titers against HTLV-1 in the sera of mice were measured using a particle agglutination kit. (B) Splenic lymphocytes were isolated from the mice and stimulated with anti-CD3 in vitro. Production of mouse IL-2 was measured by sandwich immunoglobulin ELISA. *Mice infected IP exhibited higher IL-2 production than mice infected IV or PO or than uninfected mice (IV, p<0.01; PO, p<0.01; control, p<0.05; Welch's t-test).
Figure 2.
Figure 2.
Detection of MT-2 genomic sequences in mice. (A) Four-week-old BALB/c mice were inoculated with 107 MT-2 cells intraperitoneally and sacrificed 12 h after infection. DNA was isolated from peripheral blood mononuclear cells (PBMC), thymus, spleen and mesenteric lymph nodes, and subjected to PCR amplification using primers specific for the sequence flanking the 3′LTR of the HTLV-1 provirus in human MT-2 cells, followed by agarose gel electrophoresis. To verify template DNA, control PCR amplification reactions were performed using primers specific for human endogenous retrovirus-R (HERV-R) and mouse c-myc. The HERV-R amplification products were verified by Southern blot analysis using a digoxigenin-labeled HERV-R-specific probe. (B) BALB/c mice were inoculated with MT-2 cells intraperitoneally (IP), intravenously (IV) and perorally (PO) and sacrificed 1 month after infection. Analysis of MT-2-specific and control DNA sequences was performed as in A. Samples were subjected to agarose gel electrophoresis, and a representative image is shown.
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