Dynamics of antiretroviral restriction factor expression in sheep naturally infected with Small ruminant lentivirus (SRLV)

Small Ruminant Lentiviruses (SRLV) cause persistent, slowly progressive infections in sheep and goats, characterized by high genetic variability and a fluctuating immune response that hinders accurate diagnosis and, consequently, effective control. In this study, we monitored the dynamics of SRLV infection and the expression of antiretroviral restriction factors in a flock of 47 ewes over a 16-month period. Six serial samplings were conducted to assess antibodies detection, cell-associated viral RNA load, proviral DNA load, and gene expression of the APOBEC3 Z1, Z3, and BST2 (tetherin) proteins using absolute qPCR quantification. BST2 expression was consistently detected across most animals and sampling points, whereas APOBEC3 Z1 and Z3 showed intermittent expression patterns over time. Viral RNA load was positively associated with APOBEC3 Z1 expression, whereas APOBEC3 Z3 expression was inversely associated with proviral load, suggesting distinct and potentially opposing roles of these restriction factors during SRLV infection. Notably, viral RNA was frequently detected in the absence of detectable provirus or antibodies, indicating the presence of transient or early infection states under natural conditions. These findings highlight the dynamic involvement of the innate antiviral immune response and show the potential role of restriction factors as modulators of SRLV infection and provide new insights into host-virus interactions in naturally infected sheep.