Makhsous Negar, Goya Stephanie, Avendaño Carlos, Rupp Jason, Kuypers Jane, Jerome Keith R, Boeckh Michael, Waghmare Alpana, Greninger Alexander L
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, 98102, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, 98109, USA.
bioRxiv. 2023 May 11:2023.05.11.540440. doi: 10.1101/2023.05.11.540440.
Human rhinovirus (HRV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how HRV evolves within hosts during infection.
We sequenced HRV complete genomes from 12 hematopoietic cell transplant patients with prolonged infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL) specimens. Metagenomic (mNGS) and amplicon-based NGS were used to study the emergence and evolution of intra-host single nucleotide variants (iSNVs).
Identical HRV intra-host populations in matched NW and BAL specimens indicated no genetic adaptation is required for HRV to progress from URT to LRT. Microbial composition between matched NW and BAL confirmed no cross-contamination during sampling procedure. Coding iSNVs were 2.3-fold more prevalent in capsid over non-structural genes, adjusted for length. iSNVs modeled onto HRV capsid structures were significantly more likely to be found in surface residues, but were not preferentially located in known HRV neutralizing antibody epitopes. Newly emergent, serotype-matched iSNV haplotypes from immunocompromised individuals from 2008-2010 could be detected in Seattle-area community HRV sequences from 2020-2021.
HRV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, HRV sequences.
在免疫功能低下的个体中，人鼻病毒（HRV）感染可从上呼吸道（URT）进展至下呼吸道（LRT），导致高致死率的肺炎。关于HRV在感染过程中如何在宿主体内演变，目前知之甚少。
我们对12例造血细胞移植患者的HRV全基因组进行了测序，这些患者感染时间长达190天，样本取自上呼吸道（鼻洗液，NW）和下呼吸道（支气管肺泡灌洗，BAL）。采用宏基因组学（mNGS）和基于扩增子的NGS来研究宿主内单核苷酸变异（iSNV）的出现和演变。
匹配的NW和BAL样本中相同的HRV宿主内群体表明，HRV从上呼吸道进展至下呼吸道无需基因适应。匹配的NW和BAL之间的微生物组成证实了采样过程中没有交叉污染。经长度校正后，编码iSNV在衣壳中的流行率是非结构基因的2.3倍。模拟到HRV衣壳结构上的iSNV在表面残基中更有可能被发现，但并非优先位于已知的HRV中和抗体表位。2008 - 2010年免疫功能低下个体中新出现的、血清型匹配的iSNV单倍型可在2020 - 2021年西雅图地区社区HRV序列中检测到。
免疫功能低下宿主中的HRV感染可从上呼吸道进展至下呼吸道，无需特定的进化要求。衣壳蛋白具有最高的变异性，并且新发突变可在其他（包括未来的）HRV序列中检测到。
