Oropharyngeal group A streptococcal colonization disrupts latent Epstein-Barr virus infection.
Epstein-Barr virus (EBV) infects >90% of the human population within the first 2 decades of life and establishes reversible latent infection in B cells. The stimuli that lead to switching from latent to lytic EBV infection in vivo are still elusive. Group A streptococci (GAS) are a common cause of bacterial pharyngotonsillitis in children and adolescents and colonize the tonsils and pharynx of up to 20% of healthy children. Thus, concomitant presence of EBV and GAS in the same individual is frequent. Here, we show that EBV carriers who are colonized with GAS shed EBV particles in higher numbers in their saliva, compared with EBV carriers not colonized with GAS. Messenger RNA levels of the master lytic regulatory EBV gene BZLF1 were more frequently detected in tonsils from EBV carriers colonized with GAS than from EBV carriers not colonized. Heat-killed GAS, potentially mimicking GAS colonization, elicited lytic EBV in latently infected lymphoblastoid cell lines (LCLs) partially via Toll-like receptor 2 triggering, as did purified GAS peptidoglycan. Thus, colonization by GAS might benefit EBV by increasing the EBV load in saliva and thereby enhancing the likelihood of EBV spread to other hosts.
Experimental Infectious Diseases and Cancer Research, Division of Infectious Diseases and Hospital Epidemiology.
Seigo
S
Ueda
Satoshi
S
Uchiyama
Tarik
T
Azzi
Claudine
C
Gysin
Christoph
C
Berger
Michele
M
Bernasconi
Yasuaki
Y
Harabuchi
Annelies S
AS
Zinkernagel
David
D
Nadal
D000293:Adolescent; D002353:Carrier State / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D060085:Coinfection / Q000382:microbiology* / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D056265:Microbial Interactions; D009960:Oropharynx / Q000382:microbiology*; D014066:Palatine Tonsil / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012463:Saliva / Q000821:virology; D013290:Streptococcal Infections / Q000150:complications / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000302:isolation & purification / Q000502:physiology; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics; D017735:Virus Latency; D017201:Virus Shedding
C063676:BZLF1 protein, Herpesvirus 4, Human; D012333:RNA, Messenger; D015534:Trans-Activators
Epstein-Barr virus (EBV); TLR2; group A Streptococci (GAS); latent; lytic; oropharynx; salivary shedding; tonsil