Identification of Occult Simian T-Cell Leukemia Virus Type 1 Infection in Japanese Macaques

BACKGROUND: Primate T-cell leukemia virus type 1 (PTLV-1) is classified into a genus 𝐷𝑒𝑙𝑡𝑎𝑟𝑒𝑡𝑟𝑜𝑣𝑖𝑟𝑢𝑠 that persists in infected primates and can lead to adult T cell leukemia and inflammatory diseases. Unlike hepatitis viruses, it remains unclear whether PTLV-1 could cause occult infection, a rare latent infection status characterized by detectable provirus without accompanying antibody responses. METHODS: A longitudinal study was conducted to characterize mother-to-child transmission of simian T cell leukemia virus type 1 (STLV-1) in Japanese monkeys (JMs). Stored blood samples obtained from STLV-1-infected JM mothers and their offspring were analyzed for proviral loads, antiviral antibody titers, proviral DNA sequencing, transcriptional capability, and clonality of the infected cells. RESULTS: One JM infant was found to be positive for proviral DNA without detectable anti-STLV-1 antibodies. The seronegative infection persisted for at least five years, despite positive antibody responses to other viruses that are widespread in JMs. Further analyses of the infant's blood demonstrated that (i) the provirus had no defective mutations, (ii) tax mRNA expression could be induced by in vitro culture, and (iii) substantial numbers of heterogeneous clones of STLV-1-infected cells were undergoing sequential turnover. In an additional retrospective study of a large JMs cohort, three out of 36 offspring of STLV-1-infected mothers were found to be persistently infected with STLV-1 without seroconversion. CONCLUSION: Our findings demonstrate that maternal STLV-1 transmission can occasionally persist for years without seroconversion. This represents the first discovery of occult infection in the genus 𝐷𝑒𝑙𝑡𝑎𝑟𝑒𝑡𝑟𝑜𝑣𝑖𝑟𝑢𝑠.