IFITM2

SARS-CoV-2依赖于具有广泛抗病毒作用的干扰素诱导人类跨膜蛋白，以进入人类细胞并在其中复制。 在一项新的研究中，来自德国乌尔姆大学的研究人员发现SARS-CoV-2依赖于具有广泛抗病毒作用的干扰素诱导人类跨膜蛋白（interferon-induced human transmembrane protein, IFITM），以进入人类细胞并在其中复制。相关研究结果近期发表在Journal of Virology期刊上，论文标题为“SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells”。 论文通讯作者、乌尔姆大学医学中心病毒学教授Frank Kirchhoff博士说，这些作者发现所有5种令人关注的SARS-CoV-2变体--- Alpha、Beta、Gamma、Delta和Omicron---“仍然强烈依赖于抗病毒跨膜蛋白，特别是IFITM2”，以有效复制并产生具有传染性的病毒后代。 Kirchhoff说，“此外，我们发现一种针对IFITM2的抗体可以保护人类肺部细胞免受SARS-CoV-2感染。我们的结果表明对于宿主导向疗法，IFITM2可能是一种非常意想不到的靶标。靶向宿主中的细胞因子，而不是病毒因子，可以减少出现病毒抗性的风险。” 这项新的研究旨在找到影响SARS-CoV-2感染的细胞因子，并深入了解先天免疫防御机制，以及病毒传播和发病机制的决定因素。(先天免疫是身体的第一道防线---检测病毒、细菌、寄生虫和毒素等入侵者，然后激活抗病毒因子和免疫细胞来攻击和摧毁这些入侵者）。 这些作者在正常IFITM蛋白水平和IFITM蛋白水平实验性下降的人类上皮肺癌细胞系中进行了SARS-CoV-2感染研究，然后通过定量确定病毒RNA和传染性病毒产生来测量病毒复制情况。此外，他们用靶向IFITM2或病毒ACE2受体[SARS-CoV-2用来进入宿主细胞的主要因子]的抗体处理人类肺部细胞，发现这两种措施都能抑制SARS-CoV-2感染。 IFITM在SARS-CoV-2变体在Calu-3细胞中复制方面的作用，图片来自Journal of Virology, 2022, doi:10.1128/jvi.00594-22。 这些作者确定IFITM蛋白是SARS-CoV-2感染的重要干扰素诱导增强剂，它们在他们分析的所有相关靶细胞中表达。Kirchhoff说，“这对我们理解SARS-CoV-2的传播和发病机制有重要意义。此外，我们的结果提供了关于SARS-CoV-2如何避免，或者在这种情况下，甚至利用先天的细胞防御机制的新见解。” 作为一名研究HIV的专家，Kirchhoff最初的方法是确定限制HIV的细胞因子是否可能对抗SARS-CoV-2。他说，“当我们认为人工过量表达IFITM会像预期的那样抑制SARS-CoV-2时，出现了一个惊人的、完全出乎意料的反差---人类肺细胞中的内源性IFITM对这种病毒的有效进入和复制至关重要。”（生物谷 Bioon.com） 参考资料： Rayhane Nchioua et al. SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells. Journal of Virology, 2022, doi:10.1128/jvi.00594-22.

Researchers from the Cleveland Clinic have uncovered a greater understanding of the underlying causative mechanisms responsible for cognitive impairment in patients with coronavirus disease 2019 (COVID-19), providing greater insight into an issue that has remained largely shrouded in uncertainty over the past year. The study, published online in Alzheimer’s Research & Therapy, used artificial intelligence to compare datasets comprising patients with COVID-19 and Alzheimer's disease (AD). The investigators reported no evidence suggesting SARS-CoV-2 directly infects the brain; however, there was evidence of network-based associations between the novel coronavirus and genes and proteins associated with AD and other neurologic conditions. Additionally, the investigators assessed possible relationships between COVID-19 and neuroinflammation and brain microvascular injury – two hallmarks of AD. Significant associations were found between both pathways implicated in dementia. Also, the investigators detected abnormal AD biomarker expression in cerebrospinal fluid and blood of patients who had COVID-19. Elevated expression of BSG and FURIN, two SARS-CoV-2 host factors, as well as antiviral defense genes LY6E, IFITM2, IFITM3, and IFNAR1 were observed in the brain endothelial cells of patients with AD as well as healthy controls compared with neurons and other types of cells. The researchers wrote that this finding suggests brain microvascular injury plays a potential role in COVID-19-mediated cognitive impairment. In addition, patients with APOE E4/E4, the AD risk allele, demonstrated evidence of reduced antiviral defense gene expression compared with patients who carried APOE E3/E3, indicating “a lack of expression of these genes and potentially an elevated risk of SARS-CoV-2 infection” in these patients. "We discovered that SARS-CoV-2 infection significantly altered Alzheimer's markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier," according to a statement made by lead study author Feixiong Cheng, PhD, an assistant staff at Cleveland Clinic's Genomic Medicine Institute. "These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzheimer's disease-like cognitive impairment." These new research findings immediately follow other recent studies in so-called COVID-19 “long haulers,” many of whom have frequently complained of “brain fog” and other cognitive issues. In one of those studies, published in The Lancet Psychiatry, researchers found that out of 236,379 patients who had recovered from COVID-19, approximately one out of three received a diagnosis for a neuropsychiatric condition within six months. Mood disorders were the most common diagnoses. Another study in the Annals of Clinical and Translational Neurology reported that 85% of non-hospitalized patients with long COVID-19 reported at least four long-term neurologic issues. Late last year, when the ongoing pandemic still gripped the world, researchers also found that COVID-19 could age the brain and lead to cognitive decline equivalent to the brain aging by up to 10 years. The study, which included 84,000 patients from London, suggested that the infection with the novel coronavirus was linked to significant cognitive deficits for months. It remains unclear whether these cognitive deficits are transient or permanent or if vaccines could offer hope for long-haul COVID-19. "Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the future," added Dr. Cheng.

Investigators from the Cleveland Clinic assessed possible relationships between COVID-19 and neuroinflammation and brain microvascular injury – two hallmarks of AD. Researchers from the Cleveland Clinic have uncovered a greater understanding of the underlying causative mechanisms responsible for cognitive impairment in patients with coronavirus disease 2019 (COVID-19), providing greater insight into an issue that has remained largely shrouded in uncertainty over the past year. The study, published online in Alzheimer’s Research & Therapy , used artificial intelligence to compare datasets comprising patients with COVID-19 and Alzheimer’s disease (AD). The investigators reported no evidence suggesting SARS-CoV-2 directly infects the brain; however, there was evidence of network-based associations between the novel coronavirus and genes and proteins associated with AD and other neurologic conditions. Additionally, the investigators assessed possible relationships between COVID-19 and neuroinflammation and brain microvascular injury – two hallmarks of AD. Significant associations were found between both pathways implicated in dementia. Also, the investigators detected abnormal AD biomarker expression in cerebrospinal fluid and blood of patients who had COVID-19. Elevated expression of BSG and FURIN, two SARS-CoV-2 host factors, as well as antiviral defense genes LY6E, IFITM2, IFITM3, and IFNAR1 were observed in the brain endothelial cells of patients with AD as well as healthy controls compared with neurons and other types of cells. The researchers wrote that this finding suggests brain microvascular injury plays a potential role in COVID-19-mediated cognitive impairment. In addition, patients with APOE E4/E4, the AD risk allele, demonstrated evidence of reduced antiviral defense gene expression compared with patients who carried APOE E3/E3, indicating “a lack of expression of these genes and potentially an elevated risk of SARS-CoV-2 infection” in these patients. “We discovered that SARS-CoV-2 infection significantly altered Alzheimer’s markers implicated in brain inflammation and that certain viral entry factors are highly expressed in cells in the blood-brain barrier,” according to a statement made by lead study author Feixiong Cheng, PhD, an assistant staff at Cleveland Clinic’s Genomic Medicine Institute. “These findings indicate that the virus may impact several genes or pathways involved in neuroinflammation and brain microvascular injury, which could lead to Alzheimer’s disease-like cognitive impairment.” These new research findings immediately follow other recent studies in so-called COVID-19 “long haulers,” many of whom have frequently complained of “brain fog” and other cognitive issues. In one of those studies, published in The Lancet Psychiatry , researchers found that out of 236,379 patients who had recovered from COVID-19, approximately one out of three received a diagnosis for a neuropsychiatric condition within six months. Mood disorders were the most common diagnoses. Another study in the Annals of Clinical and Translational Neurology reported that 85% of non-hospitalized patients with long COVID-19 reported at least four long-term neurologic issues. Late last year, when the ongoing pandemic still gripped the world, researchers also found that COVID-19 could age the brain and lead to cognitive decline equivalent to the brain aging by up to 10 years. The study, which included 84,000 patients from London, suggested that the infection with the novel coronavirus was linked to significant cognitive deficits for months. It remains unclear whether these cognitive deficits are transient or permanent or if vaccines could offer hope for long-haul COVID-19. “Identifying how COVID-19 and neurological problems are linked will be critical for developing effective preventive and therapeutic strategies to address the surge in neurocognitive impairments that we expect to see in the future,” added Dr. Cheng.