Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina.
Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA.
mSphere. 2023 Jun 22;8(3):e0001823. doi: 10.1128/msphere.00018-23. Epub 2023 Apr 25.
We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
我们采用诱饵富集技术进行全基因组测序，以分析导致人类汉坦病毒肺综合征的安第斯病毒（ANDV）。我们使用来自自然感染长尾 colilargo 的冷冻肺组织，包括早期、中期和晚期细胞培养、该动物分离的 ANDV 株的传代，以及实验性暴露于该 ANDV 分离株的金黄仓鼠的肺组织。对获得的完整基因组序列进行了详细的比较基因组分析，以对抗美国正粘病毒。我们确定了与细胞培养适应相关的四个氨基酸取代，这些取代导致 ANDV 在汉坦病毒肺综合征的典型致死性金黄仓鼠动物模型中减弱。ANDV 核衣壳蛋白、糖蛋白和小非结构蛋白开放阅读框的变化与与小动物模型中增加的毒力相关的 ANDV 株的突变相关。最后，我们确定了三个氨基酸取代，两个在小非结构蛋白中，一个在糖蛋白中，这些取代仅存在于与高效人际传播相关的病毒分支中。我们的研究结果表明，存在单核苷酸多态性，可以用于预测特定毒株的 ANDV 毒力和/或传染性。 几种正粘病毒在美洲引起人畜共患疾病汉坦病毒肺综合征（HPS）。其中，由安第斯病毒（ANDV）引起的 HPS 引起了极大的公共卫生关注，因为它与最高的病死率（高达 50%）有关。ANDV 也是唯一与相对可靠的人际传播证据相关的正粘病毒。这项工作揭示了 ANDV 基因组中的核苷酸变化，这些变化与动物模型中的毒力减弱和人类中的传染性增加有关。这些发现可能为未来由 ANDV 引起的 HPS 暴发提供早期严重程度预测的途径。
