继Nature之后，华南农业大学沈永义团队再发Plos Pathogens揭示马来穿山甲类新冠病毒的生物学特性

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2023-05-24 01:05

迄今为止，蝙蝠和穿山甲是已知的携带类新冠病毒的哺乳动物。2020年华南农业大学沈永义团队在Nature报道了在非法入境的马来亚穿山甲中发现了类新冠病毒，且其S蛋白的受体结合域与新冠病毒几乎完全相同。

然而，人们对其在穿山甲的致病性知之甚少。通过CT扫描，我们发现类新冠病毒阳性的马来亚穿山甲的肺部出现双侧磨片玻璃影，与新冠肺炎患者的特征相似。血气测试显示，患病穿山甲的PCO2、HCO3和TCO2水平升高，表明其呼吸困难。肺部最显著的症状是呈现出严重的间质性肺炎，其中间质和肺泡壁增厚及支气管扩张。免疫组织化学检测确认了病毒蛋白的位置跟这些病变的位置重叠。病毒感染了穿山甲的多个器官，肺是主要靶点。

转录组分析表明，病毒阳性穿山甲的干扰素反应可能不足，而细胞因子和趋化因子活性相对较高。值得注意的是，在三只穿山甲胎儿中检测到了病毒RNA和病毒蛋白，提示了该病毒在穿山甲可能存在垂直传播。该研究为更好认识该类新冠病毒在穿山甲的致病性特征提供了依据。

病毒感染穿山甲多个组织器官。（A）qRT-PCR检测。（B）WB检测。

Abstract：

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Author summary：

SARS-CoV-2 has caused a severe and ongoing global pandemic. To date, bats and pangolins are the only groups of mammals known carry SARS-CoV-2-related coronaviruses (SARSr-CoV-2). Although the SARSr-CoV-2 detected in confiscated Malayan pangolins from Guangdong, China (PCoV-GD) has lower sequence similarity to SARS-CoV-2 than some bat-derived viruses, its receptor-binding domain within the S protein that binds to host ACE2 receptors for entry into cells is almost identical to that of SARS-CoV-2. Here, we determined the pathogenicity, tissue tropism and transcriptional response of PCoV-GD in deceased adult Malayan pangolins and their fetuses. Notably, virus-positive pangolins showed ground-glass opacities in their lungs similar to COVID-19 pneumonia and blood gas tests that were indicative of dyspnea. We detected viral RNA in multiple pangolin tissues, including liver, intestine, heart, kidney, spleen and skeletal muscle. This is similar to autopsy reports in COVID-19 patients and is associated with multiple organ dysfunction syndrome. The virus-positive pangolins showed an inadequate interferon response. In addition, PCoV-GD was detected in pangolin fetuses, suggesting the potential vertical transmission of the virus in utero. In sum, Malayan pangolins infected with a PCoV-GD display a pathology that is strikingly similar to human COVID-19.

来源：病毒学界

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