HMPV/RSV co-infection: effects on replication and viral spread

呼吸道合胞病毒（RSV）和人类偏肺病毒（HMPV）是重要的呼吸道病毒， 导致显着的发病率和死亡率，特别是对于儿童、老年人和免疫功能低下的患者。 敏感的分子技术表明，呼吸道感染患者经常感染更多的病原体。 多于一种病毒病原体。在 RSV 和 HMPV 混合感染的情况下，虽然一些研究没有发现或发现有限 混合感染的影响，其他研究强烈表明 RSV-HMPV 混合感染对 病程和症状的严重程度。然而，很少有研究考察其分子细节。 这两种重要病原体同时感染。因此，RSV/HMPV 混合感染的影响仍然是一个关键因素。 继续研究的领域，但对于共同感染可能影响的机制知之甚少 病毒生命周期的步骤。通过触发先天免疫和竞争来进行病毒干扰 人们已经研究了细胞资源在共同感染中的作用，最近的研究表明，混合细胞资源 流感病毒和呼吸道合胞病毒之间可以形成病毒颗粒。 HMPV/RSV双重感染的初步研究 证明包涵体（IB）是病毒转录和复制的关键区域，可以包含 RSV 和 HMPV 基因组均存在于共同感染的细胞中，表明共享复制区室。我们的整体 假设 HMPV/RSV 共同感染会影响病毒复制和病毒传播。为了测试这一点，我们将 使用一系列实验方法和我们创造的丰富试剂来追求两个具体目标 用于检查肺炎病毒感染。首先，我们将剖析HMPV/RSV混合感染对IB的影响 形成、动力学和病毒复制，包括在感染过程中仔细分析 IB 在全局和单细胞水平上分析病毒转录和复制。其次，我们将确定 HMPV/RSV 共感染对功能性杂交病毒颗粒潜在形成的影响。此外，我们将 检查是否也利用了我们为 HMPV 描述的细胞间传播的独特途径 共同感染期间由 RSV 引起。这些重要的实验将阐明病毒共存的新分子后果 感染，提供见解，可以为其他呼吸道病毒的研究提供信息，并带来新的方法 针对呼吸道病毒感染。

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are important respiratory viruses which cause significant morbidity and mortality, particularly in pediatric, elderly and immunocompromised patients. Sensitive molecular techniques show that patients with respiratory infections are frequently infected with more than one viral pathogen. In the case of RSV and HMPV co-infections, while some studies found no or limited impact of co-infection, other research strongly indicates that RSV-HMPV co-infection has a deleterious effect on the course of disease and severity of symptoms. However, few studies have examined the molecular details of co-infection by these two important pathogens. Thus, the impact of RSV/HMPV co-infections remains a critical area for continued study, but relatively little is known about the mechanisms by which co-infections may affect the steps of the viral lifecycle. Viral interference through triggering of innate immunity and also competition for cellular resources have been studied for their roles in co-infection, and very recent work suggests that hybrid viral particles can form between influenza and RSV. Our preliminary studies of HMPV/RSV co-infection demonstrate that inclusion bodies (IBs), which are key regions for viral transcription and replication, can contain both RSV and HMPV genomes in co-infected cells, indicating a shared replication compartment. Our overall hypothesis is that HMPV/RSV co-infection affects both virus replication and virus spread. To test this, we will pursue two Specific Aims, using a range of experimental approaches and the wealth of reagents we have created for the examination of pneumovirus infection. First, we will dissect the effect of HMPV/RSV co-infection on IB formation, dynamics and viral replication, including careful analysis of IBs over the course of infection and analysis of viral transcription and replication at the global and single cell level. Second, we will determine the effect of HMPV/RSV co-infection on potential formation of functional hybrid virus particles. In addition, we will examine whether a unique pathway for cell-to-cell spread which we have characterized for HMPV is also utilized by RSV during co-infection. These important experiments will elucidate new molecular consequences of viral co- infection, providing insight that may inform studies of additional respiratory viruses and lead to new ways to target respiratory virus infections.