The Journal of pathology
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The Journal of pathology · Jul 2020
ReviewAngiotensin-converting enzyme-2 (ACE2), SARS-CoV-2 and pathophysiology of coronavirus disease 2019 (COVID-19).
Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. ⋯ In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Humans coexist with a vast bacterial, fungal and viral microbiome with which we have coevolved for millions of years. Several long recognized epidemiological associations between particular bacteria and cancer are now understood at the molecular level. ⋯ Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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The Journal of pathology · Jan 2015
ReviewTissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.
Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. ⋯ In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered.
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Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. ⋯ While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.
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The Journal of pathology · Jan 2015
ReviewPathogenesis of Middle East respiratory syndrome coronavirus.
Human coronaviruses (CoVs) mostly cause a common cold that is mild and self-limiting. Zoonotic transmission of CoVs such as the recently identified Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome (SARS)-CoV, on the other hand, may be associated with severe lower respiratory tract infection. ⋯ These findings are in line with differences in the induction of cytopathological changes, induction of host gene responses and sensitivity to the antiviral effect of interferons in vitro when comparing both MERS-CoV and SARS-CoV. The challenge will be to translate these findings into an integrated picture of MERS pathogenesis in humans and to develop intervention strategies that will eventually allow the effective control of this newly emerging infectious disease.