African swine fever virus (ASFV) is a highly infectious disease of domestic pigs, with virulent isolates causing a rapidly fatal hemorrhagic fever. In contrast, the porcine species endogenous to Africa tolerate infection. The ability of the virus to persist in one host while killing another genetically related host implies that disease severity may be, in part, modulated by host genetic variation. To complement transcription profiling approaches to identify the underlying genetic variation in the host response to ASFV, we have taken a candidate gene approach based on known signaling pathways that interact with the virus-encoded immunomodulatory protein A238L. We report the sequencing of these genes from different pig species and the identification and initial in vitro characterization of polymorphic variation in RELA (p65; v-rel reticuloendotheliosis viral oncogene homolog A), the major component of the NF-B transcription factor. Warthog RELA and domestic pig RELA differ at three amino acids. Transient cell transfection assays indicate that this variation is reflected in reduced NF-B activity in vitro for warthog RELA but not for domestic pig RELA. Induction assays indicate that warthog RELA and domestic pig RELA are elevated essentially to the same extent. Finally, mutational studies indicate that the S531P site conveys the majority of the functional variation between warthog RELA and domestic pig RELA. We propose that the variation in RELA identified between the warthog and domestic pig has the potential to underlie the difference between tolerance and rapid death upon ASFV infection.

Previous immunohistochemical studies targeting the receptor tyrosine kinase (c-Kit) have demonstrated an apparent reduction in the number of gastrointestinal pacemaker cells--the interstitial cells of Cajal (ICC)--in horses with intestinal motility disorders. This study compared the level of transcription of the c-kit gene encoding this receptor in horses with and without such motility disorders. Transcription levels of this gene were also compared to the density of ICC immunohistochemically positive for the c-Kit antigen. Intestinal samples were collected from 18 horses with intestinal disease and from 15 control animals. Following gene extraction and identification, real-time quantitative analysis of c-kit and a control gene, ACTB (β-actin), was carried out on all samples and the density of the c-Kit-positive ICC compared. There was a significant reduction in c-Kit immunoreactivity in the ICC of horses with large intestinal obstructive disorders relative to controls but no significant difference in the transcription of the c-kit gene between normal and affected animals. Further studies will be required to elucidate the mechanisms regulating c-Kit expression and to assess the pathophysiological significance of these findings.

No abstract