Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Rickettsia akari

Abstract

The effect of mouse interferon (IF) on the multiplication of Rickettsia akari in homologous (L-929) cell cultures and the effect of IF inducers on R. akari infection in mice were investigated. There was a reduction in the proportion of cells containing rickettsiae in IF-treated cultures and in the yield of rickettsiae from these cultures, as compared with those from infected cultures without IF. Trypsin treatment and heating for 1 hr at 65 C destroyed this antirickettsial activity of the IF preparation, whereas ultracentrifugation (105,000 x g for 90 min) and acidification at pH 2.0 did not affect it. There was no evidence that mouse IF inactivated R. akari directly, nor did it have an inhibitory effect on multiplication of R. akari in heterologous chick embryo cell or monkey kidney cell cultures. Susceptibility of R. akari to the action of IF was about 16 times less than that of Chlannydia trachomatis and 256 times less than the susceptibility of vesicular stomatitis virus. Mice were not protected from infection with R. akari by intraperitoneal injection with IF inducers, Newcastle disease virus (101 3 plaque-forming units/0.2 ml) or polyriboinosinic acid-polyribocytidylic acid complex (poly I:C, 200 ,pg/0.2 ml), within 24 hr before or 24 hr after intraperitoneal challenge. The yields of R. akari harvested from the spleens, livers, and peritoneal washings of infected mice treated with IF inducers were similar to those of infected control mice. Titers of IF in peritoneal washings of treated mice, taken 6 hr after administration of Newcastle disease virus or 9 hr after injection of poly I :C, were 1,024 or 320 units/ mnl, respectively. After discovery of interferon (IF; reference 5), it was first assumed that this substance inhibits only viral replication. Later, an inhibitory effect of IF on the multiplication of some nonviral intracellular parasites, such as chlamydiae (4, 12, 19) and protozoa (6, 16, 18), was demonstrated as well as the protective effect of IF inducers against bacterial infection (15, 17, 21). Some attention has also been paid to interference between rickettsiae and viruses and to a relationship between IF and rickettsiae. The ability of rickettsiae grown in cell cultures to interfere with the multiplication of viruses was demonstrated (9, 10;

Metabolism of Rickettsia typhi and Rickettsia akari in Irradiated L Cells

“…Cells infected with R. typhi (not shown) could not be distinguished from uninfected cells at the moderate magnifica- lo. g \ \+The effect of rickettsial infection on nucleic acid metabolism of the host cells was studied by the addition of trace amounts of labeled thymidine°o 8 \ ' (which was not incorporated into rickettsiae) at°\ " intervals for 2-hr periods (Fig. 6).…”

Gamma interferon as a crucial host defense against Rickettsia conorii in vivo

“…The protection against rickettsial infection afforded by IFN was observed nearly 20 years ago. It has been reported that an IFN-like inhibitor was found in mouse serum that protected mice from lethal rickettsial infection (6,7,24). In these studies, it was reported that the protective IFN was of the cta/ type.…”

Antiviral activities of interferons

“…(Suntharasamai and Rytel, 1973;Jahiel et al, 1970;Merigan, 1968, 1969); Rickettsia sp. (Kazar et al, 1971); and even bacteria Shigella flexneri (Gober et al, 1972). The sensitivities of these microbes to interferon were found to be generally less than that of virus (vesicular stomatitis virus), but mechanistically this is unrevealing as viruses can exhibit a broad spectrum of sensitivity.…”