MT-58 cells

HTLV-I can be consistently infected into rabbits, rats and squirrel monkeys (Lairmore et al., 2005). HTLV-I infectivity for rabbits was first reported by using intravenous inoculations of the MT-2 cell line (Akagi et al., 1985), a T-cell leukemia cell line established from a patient with ATL, and with the Ra-1 cell line (Miyoshi etal., 1985), a rabbit lymphocyte cell line derived from cocultivation of rabbit lymphocytes with MT-2 cells. The rabbit model has provided important information regarding the immune response against HTLV-1 infection (Cockerell et al., 1990). Establishment of a rabbit model of clinical HTLV-1 disease has been more problematic. In the majority of studies, rabbit infection has paralleled the asymptomatic infection of humans. Sporadic clinical lymphoprolif-erative disorders in HTLV-1-infected rabbits were reported (Simpson et al., 1996 Kindt et al., 2000 Zhao et al., 2002). In each of these cases, clinical disease developed after one year and usually several years after the initial infection. 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

In these models, Ki is the enzyme inhibition constant and IC90 is the concentration of inhibitor resulting in 90% inhibition of viral RNA production in HIV-infected MT-2 cells. The presence of bilinear hydrophobic terms in QSAR 2 3, where there are ahphatic variations at the P2/P2 position of 16 indicate that hydrophobic interactions are important up to a rather high value Ki 6.53, IC90 6.96). Steric interaction of the X-substituent was also found to... 

Several 1,2-cw-thiodisaccharides were evaluated for their capacity to inhibit HIV-induced cell killing and virus production in LEM or MT-2 cells. All the compounds were inactive except for the thiokojibiose octaacetate 181 (Scheme 36), but none was evaluated as an inhibitor of glucosidases I or II [37]. 

Another dideoxypyrimidine nucleoside active against human immunodeficiency vims is 3 -azido-2/3 -dideoxyuridine [84472-85-5] (AZDU or CS-87, 64) C H N O. Since its synthesis, (167) CS-87 has been identified as a promising antiHIV agent (168) and is currentiy undergoing phase I clinical trials in patients with AIDS and AIDS-related complex. It appears to be less potent than AZT against HIV in a peripheral blood mononuclear (PBM) cell screening system and in MT-4 cell lines. This lower activity in PBM cells appears to be related to a lower affinity of CS-87 for the enzyme responsible for its initial phosphorylation (169). However, CS-87 has significantly lower toxicity on bone marrow cells than AZT (170) and penetration of the CNS as a 5 -dihydropyridine derivative. 

Table 2. Anti-HIV-1 mb Activities of Macrocyclic Compounds (De Clercq s Group) in MT-4 Cells...

So far the most potent anti-HIV compounds in vitro among the macro-cyclic polyamines are dinuclear zinc(II) complex of m-xylyl-biscyclen (23) (by Kimura s group) and p-xylyl-biscyclam (30) (by De Clercq s group). They are active against various strains of HIV-1 and HIV-2, while cytotoxicity towards host MT-4 cells are minimal. Their activity against HIV is selective and they are not active against other viruses tested. Hence, the study of their mode of action is not only useful in developing... 

Antiviral activity. Ethanol (80%) extract of the dried leaf, in cell culture at a concentration of 0.2 mL/well, was equivocal on poliovims inactive on herpes virus, measles, and Semliki Forest virus and produced weak activity on coxsackie virus Pretreatment of mice with sesame extract failed to reduce the cytophatic effect of human immunodeficiency virus 1 (HlV-1) infection in MT-4 cells. No apparent acute toxicity was detected in mice with oral administration of 10 g/kg of the extract "". ... 

Anti-HIV activity of prenylflavones from mulberry tree, kuwanon H (2), morusin (3) and its derivatives, was reported by Luo et al. [117]. We studied the effect of Morns flavones on HIV-1 ms infected MT-4 cells, but no flavone showed anti-HIV activity in our screening system [111]. These discrepant results might be due to multiple acting sites of... 

Table 7. Inhibitory activity against Bacillus subtilis H17 and tec-assay (disk diffusion method) of isoprenoid-substituted phenols (75 pg/disk), their cytotoxic activities against HSC-2 and MT-4 cells, and other biological activities...

Two saponins from soybean seeds having soyasapogenol as aglycone were shown to have a partial inhibitory effect on HIV-induced cytopathology in infected human MT-2 lymphocytes cultures [158], The major constituent of group of B saponins from soybean seeds completely inhibited HIV-induced cytophatic effects and virus-specific antigen expression 6 days after infection at concentration > 0.25 mg/ml. Saponins isolated from soybean seeds inhibited HIV-1 replication in MT-4 cells at 0.5 [tg/ml (Nakamura et al. 1992) [159]. These saponins had a narrow therapeutic index and did not inhibit HIV-1 RT. One of them was found to inhibit HIV-induced cell fusion in MOLT-4 cells. 

Kern SM, Bennett RN, Needs PW, Mellon FA, Kroon PA, Garcia-Conesa MT. 2003b. Characterization of metabolites of hydroxycinnamates in the in vitro model of human small intestinal epithelium caco-2 cells. J Agric Food Chem 51 7884-7891. 

Kuhfeld MT, Mahraoui L, Rodolosse A et al. (1994) Presence and differential expression of SGLT1, Glutl, Glut2, Glut3 and Glut5 hexose transporter mRNAs in CACO-2 cell clones in relation to cell growth and glucose consumption. Biochem J 298 629-633... 

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