Identification of Natural Remission of Mother-to-Child Retroviral Transmission.

Abstract

Spontaneous remission once a retroviral infection has been established does not occur and infection persists lifelong. Stored blood samples obtained from simian T-cell leukemia virus type 1 (STLV-1)-infected Japanese macaque (JM; Macaca fuscata) mothers and their offspring during long-term follow-up as well as periodic health checkups were analyzed for proviral DNA levels, anti-STLV-1 antibody titer, DNA sequence, and viral clonality in peripheral blood mononuclear cells. We found spontaneous remission after the establishment of retrovirus mother-to-child transmission (MTCT); 3 JM infants were positive for the provirus at 5 and 8 months of age; however, no evidence of persistent STLV-1 infection was found in any of these infants thereafter up to 3 years of age. The viral env sequencing showed the presence of signature nucleotide polymorphisms, which were identical between each mother and infant but not others, suggesting STLV-1 MTCT. STLV-1-infected cells were capable of viral transmission and were composed of a heterogeneous population of clones, which were completely replaced between 5 and 8 months of age, suggesting the possibility of ongoing de novo infection from mother to infant cells. Furthermore, a retrospective study showed that 8 of 38 infants born to STLV-1-infected mothers developed transient infection comparable to the cases above. Our findings demonstrate for the first time that spontaneous remission can occur after the establishment of retroviral MTCT. Our results unveil the unique dynamics of retroviral infection during MTCT.