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Public versus personal serotypes of a viral quasispecies

机译:病毒准种的公共血清型和个人血清型

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Noncytopathic RNA viruses persist in their natural hosts at various levels as highly mutating quasispecies. They exhibit only one known serotype. In most inbred DBA/2 mice infected with 2 x 10~4 or 2 x 10~6 plaque-forming units (pfu) of lymphocytic choriomen-ingitis virus (LCMV), the virus is transiently controlled below detectable levels measured with conventional assays (<1.7 pfu), but reemerges despite a common neutralizing Ab (nAb) response. Wild-type virus and cloned mutant viruses that had escaped polyclonal nAb responses in vivo induced nAb liters in new hosts that were usually cross-reactive; some sera were highly specific for certain mutants. The few mice that controlled LCMV infection for >170 days produced not only nAb against wild-type but also variably against many other mutants isolated from other mice with reemerging viremia. When DBA/2 mice were immunized and boosted with 200 pfu of a LCMV mutant, the neutralizing Ab response was limited to the immunizing "personal" clone. Thus, in contrast to classical serotype-def ined cytopathic viruses (e.g., polio viruses) that induce strictly non-cross-reactive nAb titers, LCMV, a noncytopathic RNA virus, represents a dynamic multiplicity of personal serological submutants. Together, these mutants form a generally recognized "public" serotype. These findings may help to explain aspects of human infections and Ab responses against hepatitis B virus, hepatitis C virus, and HIV.
机译:非细胞病性RNA病毒作为高度变异的准种在各种水平的自然宿主中持续存在。它们仅表现出一种已知的血清型。在感染了2 x 10〜4或2 x 10〜6斑块形成单位(pfu)的淋巴细胞性脉管膜炎病毒(LCMV)的大多数近交DBA / 2小鼠中,该病毒被暂时控制在常规检测方法检测到的可检测水平以下( <1.7 pfu),但尽管出现中和的Ab(nAb)反应,但仍会重新出现。逃脱了体内多克隆nAb反应的野生型病毒和克隆突变病毒在通常具有交叉反应性的新宿主中诱导了nAb升。一些血清对某些突变体具有高度特异性。少数控制LCMV感染> 170天的小鼠不仅针对野生型产生了nAb,而且还针对从其他具有新生病毒血症的小鼠分离出的许多其他突变体产生了变异。当对DBA / 2小鼠进行免疫并用200 pfu的LCMV突变体加强免疫后,中和的Ab反应仅限于免疫的“个人”克隆。因此,与严格限定非交叉反应性nAb效价的经典血清型限定的细胞病病毒(例如,脊髓灰质炎病毒)相反,LCMV,一种非细胞病性RNA病毒,代表了个人血清亚突变体的动态多样性。这些突变体一起形成了公认的“公共”血清型。这些发现可能有助于解释人类感染的方面以及针对乙型肝炎病毒,丙型肝炎病毒和HIV的抗体反应。

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