Early establishment of γ-herpesvirus latency:: Implications for immune control
Early establishment of γ-herpesvirus latency:: Implications for immune control
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DOI：
10.4049/jimmunol.174.8.4972
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Blackman, MA
中科院分区：
文献类型：
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作者：
Flaño, E;Jia, QM;Blackman, MA
人类γ-疱疹病毒、EBV和卡波西肉瘤相关疱疹病毒感染全世界> 90%的人群，并且潜伏感染与许多恶性肿瘤相关。合理的疫苗接种和治疗策略需要了解初始无症状感染期间病毒与宿主的相互作用。原发性EBV感染与上皮部位的病毒复制和进入循环B淋巴细胞池有关。病毒利用B细胞的生命周期，潜伏期在静息记忆B细胞中长期维持。在这项研究中，使用小鼠γ-疱疹病毒模型，我们证明了潜伏病毒在感染部位的早期优势，肺B细胞几乎立即感染后携带病毒。这些数据加强了B细胞不仅在感染后期而且在初始感染早期的中心作用。裂解性复制的早期抑制不影响潜伏感染的进展，并且在用复制缺陷型突变病毒感染后在淋巴组织中建立潜伏期。这些数据表明，裂解病毒复制不是体内γ-疱疹病毒潜伏期的必要条件，并表明病毒潜伏期可以通过细胞增殖传播。这些观察结果强调，预防性疫苗接种策略必须针对感染部位的潜伏性γ-疱疹病毒。
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.