Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a pandemic. Paucity of information concerning the virus and therapeutic interventions have made SARS-CoV-2 infection a genuine threat to global public health. Therefore, there is a growing need for understanding the molecular mechanism of SARS-CoV-2 infection at cellular level. To address this, we undertook a systems biology approach by analyzing publicly available RNA-seq datasets of SARS-CoV-2 infection of different cells and compared with other lung pathogenic infections. Our study identified several key genes and pathways uniquely associated with SARS-CoV-2 infection. Genes such as interleukin (IL)-6, CXCL8, CCL20, CXCL1 and CXCL3 were upregulated, which in particular regulate the cytokine storm and IL-17 signaling pathway. Of note, SARS-CoV-2 infection strongly activated IL-17 signaling pathway compared with other respiratory viruses. Additionally, this transcriptomic signature was also analyzed to predict potential drug repurposing and small molecule inhibitors. In conclusion, our comprehensive data analysis identifies key molecular pathways to reveal underlying pathological etiology and potential therapeutic targets in SARS-CoV-2 infection.

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Abnormal levels of High temperature requirement A1 (HtrA1) protein have been repeatedly observed in sera and placentas of preeclampsia patients. To understand the functions of HtrA1 in placentation and in the etiology of preeclampsia, we established HtrA1(-/-) mice. HtrA1(-/-) mice show intrauterine growth retardation, and their placentas are small due to a reduced size of the junctional zone and aberrant vascularization in the labyrinth at the mid-gestation stage. HtrA1 is expressed by Tpbpa-positive trophoblast precursors in the outer ectoplacental cone and junctional zone from embryonic day 7.5 to 10.5. In the HtrA1(-/-) placenta, Tpbpa-positive cell precursors are decreased in the early stage. Spongiotrophoblasts and glycogen trophoblast cells, both of which differentiate from Tpbpa-positive precursors, are consequently decreased in the junctional zone. Fewer spiral artery-associated trophoblast giant cells, another cell type derived from Tpbpa-positive precursors, invade the decidua and associate with maternal arteries in the HtrA1(-/-) placenta than in the wild type placenta. Maternal arteries in the HtrA1(-/-) decidua have narrower lumens, thicker arterial walls, and more vascular smooth muscle cells remaining in the walls than those in the wild type decidua, indicating impaired remodeling of maternal arteries. These results indicate that HtrA1 plays important roles in the differentiation of trophoblasts from Tpbpa-positive precursors in the ectoplacental cone. Insufficient levels of HtrA1 cause poor placental development and intrauterine growth retardation, due to aberrant trophoblast differentiation and consequent defects in maternal artery remodeling, and may contribute to the onset of preeclampsia.

While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus.