Infection of rats with HTLV‐1: A small‐animal model for HTLV‐1 carriers

Abstract

A human T-cell line producing human T-cell leukemia virus type I (HTLV-I), MT-2, was injected intravenously into female F344 rats aged 5 weeks to make HTLV-I carrier rats. Antibody against HTLV-I was detected at the 5th week after MT-2 injection, and its titer reached a high plateau which continued from the 15th to the 27th week. The antibodies were against p19, p24, p28 and p53 of HTLV-I antigens from MT-2 cells. The gag, pX and LTR nucleotide sequences of HTLV-I provirus were demonstrated by using polymerase chain reaction (PCR) in the peripheral-blood mononuclear cells of 3 rats at the 44th week and 2 at the 66th to 68th week out of 8 F344 rats injected with MT-2 cells. Quantification of the HTLV-I proviral sequence revealed that 30 to 60 molecules were present in 10(5) peripheral-blood mononuclear cells, indicating that the rats were chronically infected with HTLV-I. HTLV-I-infected rats could serve as a small-animal model for studying the pathophysiological state of HTLV-I carriers and also that of HTLV-I infection on various HTLV-I-related diseases, including adult T-cell leukemia and HTLV-I-associated myelopathy.

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

“…Experimental infection of rats with HTLV-1 was first established in 1991 (Suga et al, 1991). Although initial experimental infection was achieved with F344 rats, it was later established that there was considerable differences in the response of various rat strains to HTLV-1 infection (Ishiguro et al, 1992;Kushida et al, 1993;Ibrahim et al, 1994).…”

“…Over the past 25 years, a variety of animal models of HTLV-1, infection and transformation have provided fundamental information about viral and host determinants of this devastating malignancy (Table 1). The virus consistently infects rabbits (Akagi et al, 1985;Lairmore et al, 1992), some non-human primates (Nakamura et al, 1987;Murata et al, 1996), and to a lesser extent rats (Suga et al, 1991;Ibrahim et al, 1994). Viral transmission in mice using typical methods of infection produces inconsistent infections and limited virus expression in tissues (Fang et al, 1998;Feng et al, 2001;Furuta et al, 2002a, b;Nitta et al, 2003).…”

“…The squirrel monkey has been successfully infected with HTLV-1 and offers an attractive nonhuman primate model of HTLV-1 for vaccine testing (Kazanji, 2000;Kazanji et al, 2001;Mortreux et al, 2001a;Sundaram et al, 2004). Rats have been infected with HTLV-1-producing cells and offer a tractable model of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ATL), the neurologic disease associated with the viral infection (Suga et al, 1991;Ishiguro et al, 1992;Kasai et al, 1999;Sun et al, 1999;Kannagi et al, 2000;Hakata et al, 2001). In addition, rats have been used to test the role of cell-mediated immunity to the infection (Kannagi et al, 2000;Hasegawa et al, 2003).…”

HTLV-1 tropism and envelope receptor

“…Thus, rabbit (Akagi et al, 1985;Zhao et al, 2002), rat (Suga et al, 1991;Ishiguro et al, 1992) and mouse (Fang et al, 1998;Tanaka et al, 2001) models of persistent HTLV-1 infection have been reported. In all these models, HTLV-1 was detected in a large spectrum of hematopoietic cell types and nonhematopoietic tissues, including brain, lung, kidney, heart, liver, thyroid, as well as thymic and endometrium epithelia, depending on the model and the timing of the inoculation.…”

The neutralizing function of the anti-HTLV-1 antibody is essential in preventing in vivo transmission of HTLV-1 to human T cells in NOD-SCID/¿cnull (NOG) mice

“…This will require the development of a small animal model that can be exploited as a tool for the screening and evaluation of HTLV-1 infection. However, although HTLV-1 consistently infects rabbits [2,3], some non-human primates [4,5], and to a lesser extent, rats [6,7], the virus does not efficiently infect murine cells. Previous studies have indicated that viral transmission in mice, using typical methods of infection, results in inconsistent infections and limited virus expression in tissues [8][9][10].…”