Transformed cell-specific induction of apoptosis by porcine circovirus type 1 viral protein 3.

Several members of the family Circoviridae have been shown to encode proteins with apoptotic activity. For example, both porcine circovirus type 2 (PCV2) and chicken anemia virus (CAV) encode a third viral protein (VP3) that has been shown to be cytotoxic. Interestingly, in the case of the CAV protein (designated apoptin), apoptosis is specific to transformed cell types. Similarities in genome structure and organization suggest that PCV type 1 (PCV1) may also contain a third ORF, which codes for a protein with homologous activity. To investigate this, ORF prediction followed by gene expression analyses were conducted on a gene found to be homologous to CAV and PCV2 VP3. Our data presented herein elucidate a putative ORF3 that codes for a viral protein with functional similarity to that of apoptin and PCV2 VP3. Unlike its homologues, sequence analysis revealed a highly hydrophobic, extended C-terminal domain in PCV1 VP3, which harbours a strong nuclear export signal. Subcellular localization analysis demonstrated divergent PCV1 VP3 localization patterns compared with that of CAV VP3. Interestingly, cytotoxicity studies revealed evidence that apoptosis may be selective to transformed cell types, similar to apoptin; however, PCV1 VP3 induced a dramatic G1 cell cycle arrest as opposed to the G2/M arrest observed with apoptin. These results indicate that nuclear localization of PCV1 VP3 is necessary neither for induction of apoptosis nor for transformed cell selectivity, and suggest a mechanism of action distinct from that of apoptin.

Pharmacogenomics Education Improves Pharmacy Student Perceptions of Their Abilities and Roles in Its Use.

Objective. To assess whether a required first-year course, Principles in Genetics and Pharmacogenomics, and integration into subsequent courses affected pharmacy students' perceptions of pharmacogenomics. Methods. A survey was distributed to Professional Year (PY) 1 students during the first and last weeks of the course from 2014 to 2016. A follow-up survey was distributed to PY2, PY3, and PY4 students. Results. Respondents consistently agreed that pharmacogenomics is clinically relevant. After the course, PY1 students are more comfortable in their knowledge and role in the application of pharmacogenomics. Although their comfort reverts to some degree, PY2-PY4 students believe that they should be able to apply pharmacogenomics clinically. Most PY2-PY4 students indicate that later courses review pharmacogenomics. Conclusion. A required course in genetics and pharmacogenomics can promote a perception that pharmacists should have knowledge of, and be involved in the use of genetic information clinically. Inclusion of pharmacogenomic concepts in subsequent curricular components may help in maintaining these perceptions.