Herpesvirales is an ancient viral order that infects species ranging from mollusks to humans, with lifelong persistence. They export their capsids from the nucleus to the cytoplasm by a noncanonical nuclear egress route that involves capsid budding at the inner nuclear membrane followed by fusion of this temporary envelope with the outer nuclear membrane. Here, using a whole-genome CRISPR screen, we identified ER protein CLCC1 as important for the fusion stage of nuclear egress herpes simplex virus 1. We also found that the genomes of Herpesvirales that infect mollusks and fish encode CLCC1 genes acquired from host genomes via horizontal gene transfer. In uninfected cells, loss of CLCC1 causes a nuclear blebbing defect, suggesting a role in host nuclear export. We hypothesize that CLCC1 facilitates an ancient cellular membrane fusion mechanism that Herpesvirales have hijacked or co-opted for capsid export. Structural analysis suggests that CLCC1 oligomerization into membrane-bound rings could promote membrane remodeling.

Background: Multiple case reports have pointed toward uncharacterized oral lesions, such as pulpitis, higher plaque index, necrotizing/desquamative gingivitis and others, in COVID-19 patients, suggesting that SARS-CoV-2 may worsen the manifestations of at least some oral viral infections. Our hypotheses were that COVID-19 would make oral manifestations of viral infections more common and that vaccination against Sars-CoV-2 might protect from developing such manifestations. Methods: We carried out a single-center, retrospective study, including patients from a dental and oral surgery center, studying adult and elderly patients with or without COVID-19 infection and vaccination. Results: As expected, Sars-CoV-2 infection was significantly less common among patients who received full vaccination against COVID-19: odds ratio 0.23, p< 0.001. In addition, herpetic gingivostomatitis was also less common among patients who received vaccination against COVID-19: odds ratio 0.18, p = 0.023. Developing COVID-19 itself did not have any significant correlation with developing herpetic gingivostomatitis: odds ratio 0.86, p = 0.9. Conclusions: We found that vaccination against Sars-CoV-2 markedly decreased the incidence of COVID-19 in our cohort of patients visiting a dentist’s office. In addition, such vaccination also decreased the rate of herpetic gingivostomatitis, while COVID-19 itself had no effect on it. COVID-19 itself, and vaccination against COVID-19, had no effect on the occurrence of oral manifestations of infectious mononucleosis or herpangina.