until recently, it was unknown exactly how attachment and entry into these cells was achieved. Research has shown that PCV utilizes clathrin-mediated endocytosis to enter the cell, though it's stipulated that there may still be other factors that haven't been identified. Once endocytosed, the endosome and lysosome formation causes an acidic pH shift, which allows ATP-driven uncoating of the virus and allows it to escape the endosomes and lysosomes. After the virus escapes the endosomes and lysosomes, it travels to the nucleus through unknown means. Escape Besides ORF1 and ORF2, there is also an ORF3 which is not necessarily required for PCV to survive within the host. Research has shown that the protein coded in ORF3 can modulate the host cell's cell-division cycle and cause cell-mediated, virus-induced apoptosis. Using a yeast two-hybrid screening system of ORF3 against the porcine cDNA library indicated that the ORF3 protein interacts with the porcine pPirh2, which is an E3 ubiquitin ligase. This E3 ubiquitin ligase normally interacts with p53 during the cell division cycle and prevents it from halting the cell division cycle at S-phase. However, ORF3 also interacts with pPirh2 at the same region as p53 and causes an upregulation of p53 expression. This increase in p53 stops the cell division cycle and the result of this is p53 mediated apoptosis, which releases PCV into the extracellular environment. Contamination in human vaccine On March 22, 2010, the U.S. Food and Drug Administration (FDA) recommended suspending the use Rotarix, one of two vaccines licensed in the United States against rotavirus, due to findings of viral DNA contamination. Follow-up work by GlaxoSmithKline confirmed the contamination in working cells and the viral "seed" used in Rotarix production, also confirming the material was likely present since the early stages of product development, including the clinical trials for FDA approval. Testing of the other licensed vaccine against rotavirus infection, RotaTeq, also detected some components of both PCV-1 and PCV-2. Porcine circovirus 1 is not known to cause disease in humans or other animals. As of June 8, 2010, the FDA has, based on a careful review of a variety of scientific information, determined it is appropriate for clinicians and public health professionals in the United States to use both Rotarix and RotaTeq vaccine. See also Animal virology References External links The Control of Porcine Circovirus Diseases (PCVDs): Towards Improved Food Quality and Safety Animal Disease Diagnostic Laboratory Porcine