The 2019 novel coronavirus is one of seven members of this family known to infect humans, and the third in the past three decades to jump from animals to humans.
Coronaviruses are made up of one strip of RNA, and that genetic material is surrounded by a membrane studded with little spike proteins. (Under a microscope, those proteins stick up in a ring around the top of the virus, giving it its name—“corona” is Latin for “crown.”) When the virus gets into the body, those spike proteins attach to host cells, and the virus injects that RNA into the cell’s nucleus, hijacking the replication machinery there to make more virus. Infection ensues.
The severity of that infection depends on a couple factors. One is what part of the body the virus tends to latch on to. Less serious types of coronavirus, like the ones that cause the common cold, tend to attach to cells higher up in the respiratory tract —places like your nose or throat. But their more gnarly relatives attach in the lungs and bronchial tubes, causing more serious infections. The MERS virus, for example, binds to a protein found in the lower respiratory tract and the gastrointestinal tract, so that, in addition to causing respiratory problems, the virus also often causes kidney failure.
The other thing that contributes to the severity of the infection is the proteins the virus produces. Different genes mean different proteins; more virulent coronaviruses may have spike proteins better at latching onto human cells. Some coronaviruses produce proteins that can fend off the immune system, and when patients have to mount even larger immune responses, they get sicker.
EDITOR’S NOTE: the WIRED source article is excellent and readable. Go to the source article for even more well-explained detail.
Zoonotic coronaviruses, ones that hopped from animals to humans like SARS and MERS, can spark a viral-induced fire throughout many of a person’s organs, and the new disease, COVID-19, is no exception when it is severe.
But what actually happens to your body when it is infected by the coronavirus? The new strain is so genetically similar to SARS that it has inherited the title SARS-CoV-2. So combining early research on the new outbreak with past lessons from SARS and MERS can provide an answer. From blood storms to honeycomb lungs, here’s an organ-by-organ look at how COVID-19 harms humans.
FULL STORY: National Geographic
Tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy.
MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at four days after infection. Double immunolabeling demonstrated epithelial cells expressing cytokeratin (CK)-18 to be the prevailing target cell of MERS-CoV. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss.
SOURCE: Scientific Reports
SARS-CoV primarily infects epithelial cells within the lung.
The virus is capable of entering macrophages and dendritic cells but only leads to an abortive infection. Despite this, infection of these cell types may be important in inducing pro-inflammatory cytokines that may contribute to disease. In fact, many cytokines and chemokines are produced by these cell types and are elevated in the serum of SARS-CoV infected patients. The exact mechanism of lung injury and cause of severe disease in humans remains undetermined. Viral titers seem to diminish when severe disease develops in both humans and in several animal models of the disease. Furthermore, animals infected with rodent-adapted SARS-CoV strains show similar clinical features to the human disease, including an age-dependent increase in disease severity. These animals also show increased levels proinflammatory cytokines and reduced T-cell responses, suggesting a possible immunopathological mechanism of disease.
SOURCE: Methods in Molecular Biology
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Coronavirus (CoV) infection is usually detected by cellular sensors, which trigger the activation of the innate immune system. Nevertheless, CoVs have evolved viral proteins that target different signaling pathways to counteract innate immune responses. Some CoV proteins act as antagonists of interferon (IFN) by inhibiting IFN production or signaling. After CoV infection, potent cytokines relevant in controlling virus infections and priming adaptive immune responses are also generated. However, an uncontrolled induction of these proinflammatory cytokines can lead to pathogenesis and disease severity as described for SARS-CoV and MERS-CoV.
The cellular pathways mediated by interferon regulatory factor (IRF)-3 and 7, activating transcription factor (ATF)-2/jun, activator protein (AP)-1, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NF-AT), are the main drivers of the inflammatory response triggered after viral infections, with NF-κB pathway the most frequently activated.
The relatively small E protein elicits a strong influence on the interaction of SARS-CoV with the host. After infection with viruses in which this protein has been deleted, increased cellular stress and unfolded protein responses, apoptosis, and augmented host immune responses were observed. In contrast, the presence of E protein activated a pathogenic inflammatory response that may cause death in animal models and in humans.
The modification or deletion of different motifs within E protein is sufficient to attenuate the virus. A comprehensive collection of SARS-CoVs in which these motifs have been modified elicited full and long-term protection even in old mice, making those deletion mutants promising vaccine candidates.
The E protein affects virus morphogenesis, budding, assembly, intracellular trafficking, and virulence. In fact, E protein is responsible in a significant proportion of the inflammasome activation and the associated inflammation elicited by SARS-CoV in the lung parenchyma. This exacerbated inflammation causes edema accumulation, leading to acute respiratory distress syndrome (ARDS) and, frequently, to the death of infected animal models or human patients.
SOURCE: Virus Research
Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver.
Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus.
There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441-700 of the spike protein (S protein) as the major epitope.
SOURCE: Current Opinion in Immunology