Respiratory Syncytial Virus Infection Pathway

Infection with human respiratory syncytial virus (hRSV) is transmitted through close contact, fomites, and aerosolized droplets. RSV first infects the epithelial lining of the upper respiratory tract and nasopharynx where the virus begins to replicate, and from there it may spread to the lower respiratory tract - bronchioles and alveoli - especially in infants. Immune response to RSV infection increases mucus production which, in combination with inflammation, leads to the narrowing of airways and bronchiolitis. Experimental vaccination with a formalin-inactivated RSV has been associated with vaccine-enhanced disease, which has hindered vaccine development and led to advancement of costly and modestly effective therapies based on monoclonal antibodies (mAb) and small molecules, which act to block RSV entry and have been reserved for high-risk patients (reviewed in Battles and McLellan 2019, and Pandya et al. 2019). Recently, a prophylactic mAb Nirsevimab was approved for use in all infants (reviewed in Keam 2023). Some of the preF vaccines, which elicit immune response against the pre-fusion conformation of the F protein (pre-F), are in the late stages of clinical trial or undergoing approval for being used in elderly patients and pregnant women (reviewed in Jenkins et al. 2023).<br><br>RSV is classified into two distinct subtypes, RSV A and RSV B, predominantly based on antigenic and sequence-based variations in the viral envelope protein G, involved in virus attachment to the host cells. Multiple RSV genotypes are often in co-circulation with a dominance shift between RSV A and RSV B subtypes occurring every 1-2 years. The majority of RSV molecular studies use a limited number of historical isolates, the so-called laboratory strains, of which hRSV A substrain A2 is the most commonly used. If not indicated otherwise, the events described in this pathway refer to findings from hRSV A2-based studies.<br><br>For review, please refer to Battles and McLellan 2019, and Pandya et al. 2019.

人类呼吸道合胞病毒（hRSV）感染主要通过密切接触、接触污染物和气溶胶化飞沫传播。该病毒首先感染上呼吸道黏膜层和鼻咽部，病毒复制即在此处开始，并可能由此蔓延至下呼吸道，即细支气管和肺泡，尤其是婴幼儿群体。对hRSV感染的免疫反应会增加粘液的产生，与炎症相结合导致气道和细支气管狭窄，引发支气管炎。使用福尔马林灭活的hRSV进行的实验性疫苗接种与疫苗增强性疾病相关联，这阻碍了疫苗的研发，并导致了基于单克隆抗体（mAb）和小分子药物的高成本且疗效有限的疗法的推进，这些药物的作用是阻断RSV的进入，并仅限于高风险患者使用（参见Battles和McLellan 2019年及Pandya等人2019年的综述）。近期，预防性单克隆抗体Nirsevimab已被批准用于所有婴儿（参见Keam 2023年的综述）。部分针对前融合构象的F蛋白（pre-F）引发免疫反应的预先融合疫苗（preF）处于临床试验后期阶段或正在申请批准用于老年人和孕妇（参见Jenkins等人2023年的综述）。

hRSV被分为两个独立的亚型，即RSV A和RSV B，主要基于病毒包膜蛋白G的抗原性和基于序列的变异，该蛋白参与病毒与宿主细胞的附着。多种RSV基因型通常共存，RSV A和RSV B亚型之间的优势地位每1-2年发生一次转变。大多数RSV分子研究使用的是有限数量的历史分离株，所谓的实验室菌株，其中hRSV A亚型A2被最广泛使用。除非另有说明，本途径中描述的事件均指基于hRSV A2的研究发现。

如需进一步了解，请参阅Battles和McLellan 2019年及Pandya等人2019年的综述。