Written by Dr. Sebastiaan Theuns, published on 18th of April 2023
Porcine circovirus 2 (PCV2) is a major viral disease affecting swine of different ages. It can cause syndromes like postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). The virus can also be responsible for reproductive problems such as SMEDI. PCV2 is present in almost all swine herds, and thus, it receives a lot of attention from veterinarians. As a consequence, many requested diagnostics assays are aimed at detecting PCV2 in swine herds.
To correctly diagnose clinical PCV2 cases, it is essential to understand its replication and pathogenesis. PCV2 is a virus that has a tropism for monocytes and lymphoblasts. Interestingly, most monocyte infections are not productive (e.g. leading to infectious virus production) but may still contain high loads of PCV2 genetic material and antigens. The monocytes can transfer the virus through a cell-associated viremia to the target sites for active replication, the lymph nodes. When the lymphoid tissues are activated (e.g. by other infections), the mitotic activity of lymphoblasts is stimulated. This is a unique opportunity for PCV2 to hijack the cellular polymerase for its own benefit, namely the replication of its genome. This results in a productive viral infection, leading to lymphoid depletion and further monocyte infiltration. Pigs affected by PCV2 typically have swollen lymph nodes due to this strong lymphoid activation and PCV2 replication.
What does this imply for diagnostics? When collecting blood from pigs we do not always detect a high load of infectious virus in serum. This is because the infection in monocytes is not productive and the virus is spreading from tissue to tissue in a cell-associated viremia (eg. in contrast to PRRSV which spreads in a cell-free viremia). So be aware of the detection of ‘genetic junk’ in serum, which can especially be the case when low genome copy numbers are detected. Do not over-conclude your findings in such cases but try to supplement your analysis with additional clinical information and histopathology if you suspect a clinical PCV2 infection. In clinical PCV2 cases, the lymph nodes are full of infectious viral particles, and the genome copy numbers in qPCR will be high, reflecting the presence of real infectious virus protected by a capsid.
The question of why PathoSense does not frequently detect PCV2 in serum or other samples like tracheobronchial swabs, while qPCRs are often testing positive, is frequently asked and is already partially explained by the text above. If you understand the explanation of replication and pathogenesis, you are halfway there. With PathoSense, many of the free cells and free genetic material present in a clinical sample are discarded, which is crucial for detecting intact pathogens. This also means that free genetic material of viruses, as above called ‘genetic junk’, is also discarded. As we explained, when PCV2 genome copy numbers in serum are low, this mostly does not reflect an active replication of the virus. This means that PathoSense will typically only detect the virus above a certain threshold where the viral genome copy number (e.g., ≥10^7 genome copies) and infectivity are high. As a conclusion, when diagnosing a clinical PCV2 infection, it is crucial to focus on the analysis of the lymph nodes, preferably together with histopathology, rather than solely focusing on blood or other matrices.