Lymphocryptovirus infection in orangutans associated with interstitial and perivascular pulmonary fibrosis

Lymphocryptoviruses (LCVs), members of the Gammaherpesvirinae subfamily, are associated with chronic fibrotic diseases in humans and animals. This study investigated LCV infection in 7 orangutans (Pongo pygmaeus), including 2 recent cases with severe respiratory disease and 5 archival cases analyzed retrospectively. Comprehensive necropsies were conducted on the recent cases, and all 7 underwent histopathological evaluation, quantitative polymerase chain reaction (qPCR), and in situ hybridization (ISH). LCV was detected in 3 cases (43%) by qPCR, including the 2 recent cases and 1 archival case. The highest viral loads, as determined by the qPCR, were observed in the lungs of positive cases. Histological examination revealed significant pulmonary interstitial fibrosis and vascular remodeling in all LCV-positive cases, and type II pneumocyte hypertrophy was most prominent in an acute case. Masson's trichrome staining confirmed varying degrees of fibrosis in the pulmonary interstitium and perivascular stroma. LCV DNA, identified through ISH, was observed in alveolar macrophages, endothelial cells of pulmonary capillaries, and spindle cells within fibrotic regions of the lung and heart. Viral isolation from lung tissue in 1 recent case was successful, demonstrating cytopathic effects in Vero cells. Genetic sequencing revealed a novel LCV strain closely related to Pongo pygmaeus lymphocryptovirus-1 and Macacine lymphocryptoviruses. These findings link LCV infection to fibrotic pulmonary lesions in orangutans. Further studies are essential to elucidate the mechanisms of LCV-related disease and its implications for wildlife conservation.