Failure to detect Trichinella spiralis p43 in isolated host nuclei and in irradiated larvae of infected muscle cells which express the infected cell phenotype.

Infection by Trichinella spiralis induces host muscle cells to become repositioned within the cell cycle and to lose differentiated skeletal muscle characteristics. Antibodies to a 43-kDa excretory-secretory (ES) protein (p43) also bind to infected host cell nuclei. Neither the identity of these nuclear antigens nor their role in inducing the infected cell phenotype is known. To address these issues, infected cell nuclei were isolated and nuclear antigens analyzed with several antibody preparations to p43. Four antibody preparations to p43 recognized 43-, 45-, 50-, 67- and 71-kDa proteins in ES extracts. The prominent proteins recognized by these antibodies in host nuclear antigen extracts were 71, 79, 86 and 97 kDa. Less prominent proteins of approximately 43 and 45 kDa were detected in nuclear extracts. However, antibodies which specifically recognized p43 failed to bind detectably with in situ and isolated host nuclei and nuclear extracts. Expression of p43 was analyzed in host cells infected by newborn larvae irradiated with 60Co. This treatment prevented expression of detectable levels of p43 in resulting muscle larvae, while infected muscle cells displayed typical infected cell characteristics. However, anti-p43 antibodies which recognized multiple ES and nuclear proteins did stain nuclei of irradiated larva-infected cells, albeit at reduced levels. The results raise doubts that p43 is required for induction of the infected cell phenotype. Nevertheless, nuclear antigens recognized by anti-p53 antibodies remain as candidates for influencing this phenotype.

Trichinella spiralis: inhibition of muscle larva growth and development is associated with a delay in expression of infected skeletal muscle characteristics.

Infection of skeletal muscle cells by Trichinella spiralis induces host cells to reenter the cell cycle and these cells subsequently become persistently suspended in apparent G2/M. To investigate the role of the parasite in this process, parasite growth and development within the infected cell was inhibited by irradiation of newborn larvae (48 and 80 krad) prior to infection of host muscle cells. Although larvae entered skeletal muscle cells, irradiation inhibited their subsequent growth and stichosome development, including development of alpha and beta stichocytes. A distinct delay in cell cycle reentry was demonstrated for irradiated larva-infected muscle cells, indicating an interaction between parasite and host factors affecting this host process. Despite effects on stichosome development and this delay, infected muscle cells reentered the cell cycle, expressed increased levels of acid phosphatase, were inhibited in myosin heavy-chain expression, and developed collagen capsules. The results indicate that normal alpha and beta stichocyte development is not required for inducing the infected cell characteristics studied. The model system may be useful in analysis of parasite products that are candidates for regulating various aspects of the infected cell phenotype.