RESUMO
Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.
Assuntos
Herpes Simples , Herpesvirus Humano 1 , Mitocôndrias , Mitocôndrias/metabolismo , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 1/metabolismo , Humanos , Herpes Simples/metabolismo , Herpes Simples/virologia , Herpes Simples/patologia , Animais , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/patologia , Progressão da Doença , Chlorocebus aethiopsRESUMO
During infection, Herpes simplex virus type 1 (HSV-1) alters the mitochondrial structure and function of the host cell. Live-cell imaging with fluorescent reporters revealed increased mitochondrial calcium and a transient ROS enrichment after HSV-1 infection. Notably, cells co-transfected with a calcium reporter displayed smaller viral replication compartments, while those with a ROS reporter exhibited average growth of viral replication compartments. Our findings suggest that the virus-induced increase in mitochondrial calcium, followed by an increased amount of bound calcium reporter, interferes with the progression of the infection.