Tropism and molecular biology of parvoviruses

我的团队专注于病毒如何能够切换宿主(例如，从一个动物物种切换到另一个动物物种或人类)。近年来，随着SARS和禽流感病毒的出现，这一话题成为人们关注的中心。然而，我们致力于细小病毒的研究，这些病毒在最近的过去显示出有规律地跨越物种障碍(例如，在20世纪40年代突然出现在水貂身上，在20世纪70年代突然出现在狗身上，可能是来自猫病毒)。这些物种屏障的突破是重要流行病的原因。我们对猪细小病毒特别感兴趣，因为猪产品和器官用于或可能用于医疗。将猪细小病毒引入免疫抑制的人类中，将为病毒跳跃宿主和自我适应提供一个理想的环境。我们已经证明，不同的细小病毒株之间存在微小的差异，导致宿主细胞的偏好不同，并使它们发挥疫苗或致病株的作用。然而，我们不知道这些微小的化学差异可以引发对新宿主细胞的适应的机制。为此，我们已经将病毒的3D结构确定为接近原子的水平，我们正在研究这些微小的结构差异对这些病毒的分子生物学的影响。我们希望，它的理解将帮助我们更好地做好准备，如果发生这种宿主转换并随后发生大流行，而我们正处于有效抗病毒药物的开发阶段。

My team has focussed its research on how viruses are able to switch hosts (e.g., from one animal species to another or to humans). In recent years, this topic has become a centre of interest with the appearance of the SARS and avian flu viruses. We work, however, with parvoviruses which have shown in the recent past to jump regularly the species barrier (e.g., sudden appearance in mink during the 1940s and in dogs during the 1970s, probably from a cat virus). These species barrier breaches were the cause of important pandemics. We are particularly interested in pig parvoviruses since pig products and organs are or may be used in medical treatments. Introducing pig parvovirus in immunosuppressed humans would give the virus an ideal environment to jump hosts and adapt itself. We have already shown that minute differences exist among different parvovirus strains resulting in differences in preferences of host cells and making them behave as a vaccine or a pathogenic strain. However, we do not know the mechanism by which these tiny chemical differences can provoke adaptation to new host cells. For this purpose, we have determined the 3D structure of the virus to a near-atomic level and we are studying the effect that these minute structural differences have on the molecular biology of these viruses. We hope that its understanding will help us to be better prepared if such a host switch, and ensuing pandemic, occurs and we are in the development stage of effective antiviral drugs.