Early establishment of gamma-herpesvirus latency: implications for immune control.
The human gamma-herpesviruses, EBV and Kaposi's sarcoma-associated herpesvirus, infect >90% of the population worldwide, and latent infection is associated with numerous malignancies. Rational vaccination and therapeutic strategies require an understanding of virus-host interactions during the initial asymptomatic infection. Primary EBV infection is associated with virus replication at epithelial sites and entry into the circulating B lymphocyte pool. The virus exploits the life cycle of the B cell and latency is maintained long term in resting memory B cells. In this study, using a murine gamma-herpesvirus model, we demonstrate an early dominance of latent virus at the site of infection, with lung B cells harboring virus almost immediately after infection. These data reinforce the central role of the B cell not only in the later phase of infection, but early in the initial infection. Early inhibition of lytic replication does not impact the progression of the latent infection, and latency is established in lymphoid tissues following infection with a replication-deficient mutant virus. These data demonstrate that lytic viral replication is not a requirement for gamma-herpesvirus latency in vivo and suggest that viral latency can be disseminated by cellular proliferation. These observations emphasize that prophylactic vaccination strategies must target latent gamma-herpesvirus at the site of infection.
Flaño
Emilio
E
Trudeau Institute, Saranac Lake, NY 12983, USA.
Jia
Qingmei
Q
Moore
John
J
Woodland
David L
DL
Sun
Ren
R
Blackman
Marcia A
MA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D018142:Gammaherpesvirinae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology*; D006566:Herpesviridae Infections / Q000209:etiology* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D012141:Respiratory Tract Infections / Q000209:etiology / Q000276:immunology / Q000821:virology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000209:etiology* / Q000276:immunology* / Q000821:virology; D014765:Viral Vaccines / Q000276:immunology; D017735:Virus Latency; D014779:Virus Replication
D004279:DNA, Viral; D014765:Viral Vaccines