Chikungunya virus replicates in the human testis <i>ex vivo</i> and impacts peritubular myoid cells functional markers

Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for debilitating, long-lasting arthralgia and myalgia. In light of recent findings of prolonged CHIKV RNA shedding in human semen and testicular tropism in animals infected with related alphaviruses, it is imperative to investigate CHIKV's capacity to infect the human testis, an established reservoir for arboviruses like Zika, and to delineate its implications for testicular function. Using an <i>ex vivo</i> human testicular tissue model, we demonstrate that CHIKV rapidly infects peritubular myoid cells (PMCs) and a range of interstitial cells, with robust viral production peaking at day 3 before declining. Importantly, seminiferous tubule cells and isolated testicular germ cells proved nonpermissive to CHIKV infection, indicating a potential limitation for seminal shedding of virions. Infected testicular explants exhibited a broad antiviral response but limited pro-inflammatory cytokines upregulation. CHIKV replication in the testis induced apoptosis and cell death, with a marked impact on PMC markers including decreased transcriptional expression of genes crucial for PMC contractile properties and extracellular matrix production. In summary, our study highlights the susceptibility of human testicular tissue to CHIKV infection, marked by robust viral replication that primarily compromises PMC function. The observed cellular impairment and damage suggest that CHIKV infection might negatively affect key testicular functions, such as tubular contractility and sperm release. These findings warrant further investigation into semen parameters and viral shedding in CHIKV-infected men.