Δ42PD-1 enhances HIV replication and suppresses maturation of dendritic cells

Abstract

Abstract Previously, we discovered a new PD-1 isoform, which consists of a 42-base pairs loss from the start of exon 2 that is equivalent to a 14 amino acid in-frame deletion. Therefore, we named this new PD-1 isoform as Δ42PD-1. Here, we found that Δ42PD-1 was highly expressed on monocyte-derived dendritic cell (MoDC) in healthy donors, while significantly decreased in HIV patients with or without antiretroviral therapy. Consistently, in vitro assay, HIV infection suppressed Δ42PD-1 expression in total MoDCs. However, upregulation of Δ42PD-1 was observed in mature MoDC (high CD83+CD86+) after HIV infection, although the mature MoDC population was unraised, which consistent with previous report that HIV infection do not mature MoDC. Therefore, to investigate the role of Δ42PD-1 on HIV replication, Δ42PD-1 positive and negative MoDC were sorted out by FACS and infected with R5-tropic HIV (JR-CSF) respectively. Interestingly, Δ42PD-1 positive MoDC was higher susceptible to HIV than Δ42PD-1 negative MoDC. Maturation is important for dendritic cell to perform innate and adaptive immune response. Further investigation revealed that Δ42PD-1 negative MoDC had higher maturation level than Δ42PD-1 positive MoDC after LPS stimulation, which means that Δ42PD-1 may suppress DC maturation. So far, we conclude that Δ42PD-1 not only enhances HIV replication, but also suppresses dendritic cell maturation. It warrants to further study the role of Δ42PD-1 on DC-mediated immune responses during HIV infection in vivo.