CONICET | Buscador de Institutos y Recursos Humanos

Hantaviruses (genus Orthohantavirus, family Hantaviridae, Order Bunyavirales) cause two acute respiratory diseases in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). HPS is found in the Americas and is mainly caused by Sin Nombre Virus and Andes virus (ANDV), while HFRS cases are found in Europe and Asia, with the main causative agents being Puumala virus (PUUV) and Hantaan virus (HTNV), respectively. While hantaviruses are known to cause acute disease in humans, a recent case report showed that ANDV was detected in semen for 9 months after infection, suggesting that these viruses may persist long-term in the immuneprivileged testis. The aim of this study was to examine the potential of hantaviruses to infect and persist in human Sertoli cells (HSerC), which constitute the blood-testis barrier. HSerC were exposed in vitro to different hantavirus species at different multiplicities of infection, and infection was assessed by immunofluorescence (IF), Western blot, real time-qPCR, and focus forming unit assays at different time points.We found that HSerC could be infected in vitro for up to 20 days post-infection (d.p.i.) with diverse hantavirus species, including pathogenic PUUV, HTNV, and ANDV, and non-pathogenic Prospect Hill virus (PHV). Additionally, rates of infection as quantified by IF increased with time, with a peak of 40% at 7 d.p.i. for PUUV, 50% at 3 d.p.i. for HTNV, 30% at 2 d.p.i. for ANDV, and 30% at 3 d.p.i. for PHV. Further, infected HSerC secreted infectious PUUV and ANDV particles until 7 and 10 d.p.i, respectively. This study confirms that hantaviruses can infect HSerC in vitro. Further research is necessary to determine whether this is also observed in patients, potentially allowing the virus to hide and persist in immune-privileged sites, and whether this could have implications for disease transmission and/or long-term consequences.

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