Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry.IMPORTANCE Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.
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PMID:LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2. 3264 82

Viruses are associated with several human diseases that infect a large number of individuals, hence directly affecting global health and economy. Owing to the lack of efficient vaccines, antiviral therapy and emerging resistance strains, many viruses are considered as a potential threat to public health. Therefore, researches have been developed to identify new drug candidates for future treatments. Among them, antiviral research based on natural molecules is a promising approach. Phospholipases A2 (PLA2s) isolated from snake venom have shown significant antiviral activity against some viruses such as Dengue virus, Human Immunodeficiency virus, Hepatitis C virus and Yellow fever virus, and have emerged as an attractive alternative strategy for the development of novel antiviral therapy. Thus, this review provides an overview of remarkable findings involving PLA2s from snake venom that possess antiviral activity, and discusses the mechanisms of action mediated by PLA2s against different stages of virus replication cycle. Additionally, molecular docking simulations were performed by interacting between phospholipids from Dengue virus envelope and PLA2s from Bothrops asper snake venom. Studies on snake venom PLA2s highlight the potential use of these proteins for the development of broad-spectrum antiviral drugs.
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PMID:Insights into the antiviral activity of phospholipases A2 (PLA2s) from snake venoms. 3269 62

A virus is an infectious particle which generally contains nucleic acid genome (DNA or RNA inside a protein shell), except for human immunodeficiency virus (HIV). Viruses have to reproduce by infecting their host cells. Polyamines are ubiquitous compounds in mammalian cells and play key roles in various cellular processes. The metabolic pathways of polyamines have been well studied. Targeting these metabolic pathways can reduce infections caused by viruses. In the study, we systematically reviewed the association of polyamine metabolic pathways and viruses including coxsackievirus B3 (CVB3), enterovirus 71 (EV71), poliovirus (PV), Zika virus (ZKV), hepatitis C virus (HCV), hepatitis B virus (HBV), dengue virus (DENV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), Ebola virus (EBOV), marburgvirus (MARV), chikungunya virus (CHIKV), sindbis virus (SINV), Semliki Forest virus (SFV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV), human cytomegalovirus (HCMV), vesicular stomatitis virus (VSV), Rabies virus (RABV), Rift Valley fever virus (RVFV), La Crosse virus (LACV), human immunodeficiency virus (HIV), Middle East respiratory syndrome virus (MERS-CoV), and coronavirus disease 2019 (SARS-CoV-2). This review revealed that targeting polyamine metabolic pathways may be a potential approach to control human viral infection.
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PMID:Targeting Polyamine Metabolism for Control of Human Viral Diseases. 3329 37


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