Norberg Peter, Depledge Daniel P, Kundu Samit, Atkinson Claire, Brown Julianne, Haque Tanzina, Hussaini Yusuf, MacMahon Eithne, Molyneaux Pamela, Papaevangelou Vassiliki, Sengupta Nitu, Koay Evelyn S C, Tang Julian W, Underhill Gillian S, Grahn Anna, Studahl Marie, Breuer Judith, Bergström Tomas
J Virol. 2015 Jul;89(14):7133-46. doi: 10.1128/JVI.00437-15.
Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpes virus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade.
Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.
水痘带状疱疹病毒（VZV）是一种人类疱疹病毒，在初次感染时通常引起水痘，并在感觉神经节和自主神经节中建立终身潜伏感染。在生命后期，该病毒可能重新激活导致带状疱疹（HZ；也称为蛇串疮）。为预防这些疾病，一种减毒活的异源疫苗制剂vOka在全球许多国家被常规使用。最近对另一种甲型疱疹病毒传染性喉气管炎病毒的研究表明，减毒活疫苗株可在体内重组，产生有致病性的子代病毒。这些发现引发了对在有利于重组的条件下使用减毒疱疹病毒疫苗的担忧。为了研究VZV是否可能发生重组（这是VZV疫苗接种创造此类条件的一个先决条件），我们在此分析了115个完整的VZV基因组。我们的结果表明VZV频繁发生重组。因此，如果有机会，VZV似乎完全有能力进行重组，这可能对VZV疫苗的持续接种具有重要意义。虽然未发现不同进化枝间的疫苗野生型重组株，但在含有疫苗株的进化枝2中频繁检测到进化枝内重组株，这表明疫苗株在体内或细胞培养传代过程中已参与重组事件。最后，先前的部分和完整基因组研究描述了一些在系统发育上不聚类到五个已确立进化枝中任何一个的毒株。这里测序的额外VZV毒株，与先前发表的毒株相结合，使我们能够正式定义一个新的第六个VZV进化枝。
虽然已证明遗传重组在其他人类甲型疱疹病毒单纯疱疹病毒1型和2型中频繁发生，但迄今为止仅证明VZV有少数古老且孤立的近期重组事件。在本研究中，我们证明VZV也频繁发生基因重组，包括属于含有vOKA株的进化枝的毒株。
