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 造成严重的发病率和死亡率，特别是在儿科、老年人和免疫功能低下的患者中。 敏感的分子技术显示，呼吸道感染患者经常感染更多 而不是一个病毒病原体。在RSV和HMPV混合感染的情况下，尽管一些研究发现没有或仅限于 混合感染的影响，其他研究强烈表明RSV-HMPV联合感染对 病程和症状的严重程度。然而，很少有研究研究这种基因的分子细节 这两种重要病原体的混合感染。因此，RSV/HMPV混合感染的影响仍然是一个关键 值得继续研究的领域，但对合并感染可能影响的机制知之甚少 病毒生命周期的各个步骤。通过触发先天免疫和竞争 细胞资源在混合感染中的作用已被研究，最新的工作表明，杂交 病毒颗粒可以在流感和RSV之间形成。HMPV/RSV混合感染的初步研究 证明包涵体(IBS)是病毒转录和复制的关键区域，可以包含 在混合感染的细胞中，RSV和HMPV基因组都存在，这表明复制空间是共享的。我们的整体 假设HMPV/RSV混合感染既影响病毒复制又影响病毒传播。为了测试这一点，我们将 追求两个具体目标，使用一系列实验方法和我们创造的丰富试剂 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、动态和病毒复制，包括仔细分析IBS在感染过程和 全球和单细胞水平的病毒转录和复制分析。第二，我们将确定 HMPV/RSV混合感染对功能性杂交病毒颗粒形成的影响此外，我们还将 检查是否也利用了我们所描述的HMPV在细胞间传播的独特途径 在混合感染期间被RSV感染。这些重要的实验将阐明病毒协同作用的新的分子后果。 感染，提供洞察力，可能为其他呼吸道病毒的研究提供信息，并导致新的方法 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.