Paratuberculosis (Johne's disease) is a chronic, wasting, widespread mycobacteriosis of ruminants. It involves extensive mycobacterial shedding, which accounts for the high contagiousness, and ends with a fatal enteritis. Decreases in weight, milk production, and fertility produce severe economic loss. The DNA of the etiological agent (Mycobacterium paratuberculosis) has a base composition (66 to 67% G+C) within the range of that of mycobacteria (62 to 70% G+C), a size (4.4 x 10(6) to 4.7 x 10(6) bp) larger than that of most pathogenic mycobacteria (2.0 x 10(6) to 4.2 x 10(6) bp), and a high relatedness (> 90%) to Mycobacterium avium DNA. However, the DNAs of the two organisms can be distinguished by restriction fragment length polymorphism analysis. M. paratuberculosis genes coding for a transposase, a cell wall-associated protein (P34), and two heat shock proteins have been cloned and sequenced. Nucleic acid probes (two of which are species specific) are used, after PCR amplification, for M. paratuberculosis identification in stools and milk. As in leprosy, with disease progression, cellular immune reactions decrease and humoral immune reactions increase. Cutaneous testing with sensitins, lymphocyte proliferation assays, and cytokine tests are used to monitor cellular immune reactions in paratuberculosis, but these tests lack specificity. Complement fixation, immunodiffusion, and enzymometric tests based on antibodies to M. paratuberculosis extracts, to mycobacterial antigen complex A36, to glycolipids, and to proteins help identify affected cattle but are not species specific. The carboxyl-terminal portion of the 34-kDa cell wall-associated A36 protein (P34) carries species-specific B-cell epitopes and is the basis for an enzyme-linked immunosorbent assay. Diagnostic tests for paratuberculosis are also used in Crohn's disease, a chronic human ileitis mimicking Johne's disease, in which isolates identified as M. paratuberculosis have been found.

In vitro-transcribed human interferon-I3

The human '26-kd protein' is a secreted glycoprotein expressed, for example, in (blood) Here we show that the recombinant 26-kd protein exhibits a high growth factor activity when assayed on an IL-

A human‐leukocyte‐derived antiviral protein (22‐kDa factor), known to be an inducer of interferon‐β (IFN‐β) in fibroblastoid cells, and to be closely related to interleukin‐1 (IL‐1), was shown to likewise act as inducer of the mRNA of a 26‐kDa secreted protein. This protein was first described as the gene product of an mRNA that is co‐induced with the mRNA of IFN‐β by superinduction of fibroblasts (treatment with dsRNA and cycloheximide). Subsequently it was shown to be induced by treatment with cycloheximide only. The 22‐kDa factor induced high levels of the 26‐kDa‐protein mRNA and low levels of IFN‐β mRNA. Addition of cycloheximide to the 22‐kDa‐factor resulted in further significant increases in mRNA levels for both the 26‐kDa‐protein and IFN‐β. These observations add to the evidence already available that transcription of the genes for IFN‐β and the 26‐kDa‐protein are differently regulated. The observation that a factor that belongs to the IL‐1 family induces the 26‐kDa‐protein suggest that the latter plays a role as an intermediary or effector molecule in inflammatory or immunoregulatory processes.

A species-specific recombinant clone (F57) was obtained from a genomic library of Mycobacterium paratuberculosis in the transcription vector pGem 3Z. This clone proved to be specific for all mycobacteria tested, including M. avium, and was able to recognize all of the tested M. paratuberculosis strains isolated from animals and humans (patients with Crohn's disease). The F57 insert was sequenced, and a segment of 620 bp with a G+C content of 58.9%o was identified. Comparison of the sequence with sequences in the EMBL and UGEN data banks revealed the uniqueness of the F57 sequence, which had no resemblance to other known genes.