AUTHOR=Nelsen April , Lin Chun-Ming , Hause Ben M. TITLE=Porcine Parvovirus 2 Is Predominantly Associated With Macrophages in Porcine Respiratory Disease Complex JOURNAL=Frontiers in Veterinary Science VOLUME=Volume 8 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.726884 DOI=10.3389/fvets.2021.726884 ISSN=2297-1769 ABSTRACT=Porcine respiratory disease complex (PRDC) is a significant source of morbidity and mortality, manifested by pneumonia of multiple etiology where a variety of pathogens, environment, and management practices play a role in disease. Porcine reproductive and respiratory disease virus (PRRSV), influenza A virus (IAV), and porcine circovirus 2 (PCV2) are well-established pathogens in PRDC. Porcine parvovirus 2 (PPV2) has been identified in both healthy and clinically diseased pigs at a high prevalence worldwide. Despite widespread circulation, the significance of PPV2 infection in PRDC and the association with other co-infections are unclear. Here, PPV2 was detected in lung tissue in 39 of 100 (39%) PRDC-affected pigs by quantitative polymerase chain reaction (qPCR). Using in situ hybridization (ISH) in conjunction with tissue microarrays (TMA), PPV2 infection was localized in alveolar macrophages and other cells in lungs with interstitial pneumonia in 28 of 99 (28.2%) samples. Viral load tended to correlate with the number of macrophages in the lungs. Assessment of frequency, viral titers and tissue distributions showed no association between the infection of PPV2 and other major viral respiratory pathogens. In one-third of qPCR PPV2-positive samples, no other known viruses were identified by metagenomic sequencing. Genome sequences of PPV2 were 99.7% identical to reference genomes. Although intensive intra-nuclear and intra-cytoplasmic signals of PPV2 were mainly detected in alveolar macrophages by ISH, no obvious virus replication was noted in vitro cell culture. Together, these results suggest PPV2 is associated, but may not be the sole causative agent, with PRDC, warranting the control and prevention of this underdiagnosed virus.