Plos Pathogens：疱疹病毒和疟原虫或形成致命组合

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2015年6月18日/生物谷BIOON/-- 疟疾一直是困扰人类的高致死性疾病之一。患上严重疟疾的儿童大约有20%会死亡。实际上，让患上疟疾的情况更加糟糕的是，同时感染了疟原虫和其他致病菌（或寄生虫）。在非洲泛撒哈拉地区，很多婴儿在出生六个月的时候就感染了人类四型疱疹病毒（EBV）。而这个时间正好是婴儿体内来自母亲的抗体开始减弱的时候，这个阶段也很容易感染上疟原虫而患上疟疾。

近期发表在《Plos Pathogens》的研究文章称，他们发现了感染疟人类疱疹病毒（EBV）可能导致人体对疟疾的免疫能力严重下降。通常在第一二次局部区域接触恶性疟原虫并患上疟疾的时候，人体即获得免疫。再次感染疟原虫时，免疫系统会调动身体消灭这些病原体。而该课题组在实验发现，如果小鼠急性感染了非致死性人类疱疹病毒MHV68（一种非致死性的人类疱疹病毒），针对约氏疟原虫（一种非致死性疟原虫）的二次感染的免疫力严重降低，并导致这种非致死性的疟原虫成为了小鼠新的致死性威胁。

他们还发现，非致死性人类疱疹病毒MHV68的一种膜蛋白M2起了很大作用。首先，在MHV68急性感染时，这种蛋白质能够抑制宿主对该病毒的抗病毒反应。其次，在这种病毒和疟原虫共感染的情况下，宿主针对疟原虫的免疫反应的抑制与M2相关联，让非致死性的约氏疟原虫变成致命的感染源。

作者们总结道，在小鼠实验中，发现急性感染人类疱疹病毒导致针对疟原虫的免疫力下降，对人类也有重要启示。对新生儿而言，同时感染人类疱疹病毒和疟原虫会带来很高的风险。同时，在新生儿中，针对疱疹病毒的疫苗，可能也为抵抗疟疾提供新的解决方案。（生物谷Bioon.com）

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Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity
Caline G. Matar, Neil R. Anthony, Brigid M. O’Flaherty, Nathan T. Jacobs, Lalita Priyamvada, Christian R. Engwerda, Samuel H. Speck , Tracey J. Lamb

Abstract

[size=0.8125]Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primaryPlasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodiumtransmission.

Author Summary

[size=0.8125]Nearly 1 million deaths occur annually as a result of complications associated with P.falciparum infection, with children younger than 5 being the most susceptible age group. Earlier studies have demonstrated that children co-infected with P. falciparum and Epstein-Barr virus (EBV) have impaired immune responses to control EBV, and this can result in the development of a jaw tumor called endemic Burkitt’s lymphoma (eBL). It is not known if there is any impact of acute EBV infection on the generation of anti-malarial immunity. We have used mouse models of EBV [murine gammaherpesvirus 68 (MHV68)] and malaria (P. yoelii XNL) to demonstrate that acute gammaherpesvirus infection can impair the generation of antibodies that control Plasmodium parasitemia, in turn causing a non-lethal P. yoelii XNL infection to become lethal. We identify a critical role for the MHV68 M2 protein in mediating the suppressive effect of acute MHV68 infection on the generation of humoral immunity to a secondary malaria infection. This work demonstrates that gammaherpesvirus infections can suppress the generation of an effective anti-malaria immune response and suggests that acute EBV infection should be investigated as a risk factor for the development of severe malaria in young children.

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004858

ipsvirus

共感染的情况太复杂了。有些细菌与病毒共感染时也是致命的