Duran Martin
Cellular Biology
E-portfolio introduction
11/8/20
Immune response to SARS-CoV-2 protein fragments analyses
Covid-19 is a viral infection that began its spread in late 2019 and has caused millions of people across the globe to become infected and has caused considerable mortality. Effects caused by this disease can range from mild to acute illness and death.(Mateus, 2020). Coronaviruses have the biggest genome of viruses containing RNA with some 30,000 base pairs, giving them a hight rate of recombination. (Woo, 2005). The RNA genome expresses frames that code for structural and non-structural proteins. They have four structural proteins, spike, nucleocapsid, envelope, and membrane. (Satarker, Sairaj, and Nampoorthiri, 2020). Some cross reactivity was noted in SARS-CoV-2 peptides were observed prior to covid-19. Covid-19 patient serum has shown high reactivity with other pathogic H, SARS, and MERS covids. The coronaviruses that shared the most sequence identity with SARS-CoV-2 had peptides where high levels of reactvity was observed against them. (Shrock,2020). Serums from patients also showed much higher reactivity to season covid peptides compared to pre-covid-19 controls. (Shrock,2020).
The majority of people get infected with the human strains of coronaviruses, however, the illnesses usually only last for a small period of time and their symptoms include fever, cough, headache, running nose, and sore throat. All which are soft symptoms relating to the common cold. (National Foundation for Infectious Disease, 2020). Even so, SARS-CoV-2 can cause the human coronavirus covid-19 and has been reported to cause more serious acute respiratory illnesses like bronchitis or pneumonia and even death. (National Foundation for Infectious Disease, 2020). Multiple coronaviruses are known to impact the human population, also causing symptoms ranging from mild to acute. These corona viruses cause antigen and T cell reactions in patients who have become infected. Even so, antibody levels seem to drop faster than T cell levels. Antibodies specific to SARS-CoV fell below detectable ranges within 2-3 years whereas the memory T cell levels have still been detected 11 years later. (Bert, 2020)
Studies on the human immune response to SARS-CoV-2 have started to identify antigen specific T cell response and has shown marked activation of T cells in patients with covid-19. The study has also shown that between 20% and 50% of people have considerable T cell response towards peptides associated with SARS-CoV-2 sequences and they had not been exposed. (Mateus, 2020). Studies of T cell responses have also shown that CD4 and CD8 that recognize multiple regions of the N protein or the nucleocapsid protein. Strong cross reactivity against the N protein in SARS-CoV-2, COVID-19, was detected. (Bert, 2020)
It was hypothesized that the patients having T-cell response to these peptides may be related to already existing memory reactions to the human common cold coronaviruses. Some of these corona viruses include HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E. They have similar structure and physiology with the sequences of the coronavirus and are usually responsible for light symptoms affecting the respiratory symptoms. The hypothesis that this possible cross reacting T cell immunity to SARS-CoV-2 could give light to the various COVID-19 clinical results, influence the information gathered on the models of herd immunity, or impact the effectiveness of vaccines given to the subjects with the novel coronavirus. (Mateus, 2020).
Direct evidence of reactivity to common cold epitopes similar to covid-19 epitopes was in fact one of the discoveries found in this study. To detect whether reactivity to SARS-CoV-2 in subjects who weren’t exposed could be caused by cross-reactivity to other HCoVs, pools were set up containing peptides that are homologous to epitopes developed from various strands of the common cold virus and SARS-CoV-2. A procedure utilizing an activation inducer marker was conducted to discover T cells in a set of unexposed donors and a set of recovering Covid-19 patients. From these series of studies, significant T cell reactivity against SARS-CoV-2 peptides was discovered compared to the controls. The observation of T cells with peptide pools that were chosen on the basis of homology was constant with the hypothesis that cross reactive T cells between SARS-CoV-2 and various HCoVs are present in a multitude of individuals. In CD4-R30 and CD4-S31, but not HCoV-R129 and HCoV-S124, immune reactivity was increased in subjects with COVID-19 compared to those who were not exposed. Therefore, existing CD4 T cell response is activated by exposure to COVID-19 and cross-reactive SARS-CoV-2 epitopes in COVID-19. The following data from novel coronavirus cases are not consistent with the hypothesis that exposure to the common cold causes an original antigen response, at minimum for subjects with average severity of COVID-19 symptoms. (Mateus, 2020).
Memory phenotypes of T cells reacting in pools containing different kinds of epitopes were also examined. Results from those examinations showed that reacting cells in unexposed donors were mostly found in the memory CD4 T cell population, then the central memory T cells. Similar patterns of effector and central memory cells were seen in the CD4 T cells found in the COVID-19 cases. This means that CD4 T cells in unexposed subjects that react to SARS-CoV-2 epitopes, and other HCoV epitopes, have a memory phenotype. Data from these studies align with the hypothesis that CD4 T cells responding to SARS-CoV-2 epitopes in unexposed subjects also being the memory CD4 T cells in HCoV and are cross reactive to SARS-CoV-2. (Mateus, 2020).
Throughout this study, over 140 human T cells epitopes developed from the SARS-CoV-2 genome. Straightforward evidence that many CD4 T cells reacting to SARS-CoV-2 epitopes cross react with corresponding homologous sequences from the various common cold strands and that those responding cells are mainly memory CD4 T cells. These discoveries are contrary to HCoV neutralizing antibodies, which are HCoV specific antibodies and didn’t display cross reactivity to SARS-CoV-2 RBD. On the bases of the information gathered on this part of the study, it is constant with the hypothesis that already-existing cross reactive HCoV CD4 T cell memory in some subjects could be an addition to the variable results in COVID-19 patients. (Mateus, 2020).
Works Cited
1. Woo, Patrick C Y, et al. (2005) “Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia.” Journal of Virology, American Society for Microbiology, www.ncbi.nlm.nih.gov/pmc/articles/PMC538593/.
2. J. Mateus et al. (2020) Science 10.1126/science.abd3871
3. Satarker, Sairaj, and Madhavan Nampoothiri. (2020) “Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2.” Archives of Medical Research, IMSS. Published by Elsevier Inc., www.ncbi.nlm.nih.gov/pmc/articles/PMC7247499/.
4. “Coronaviruses.” National Foundation for Infectious Diseases, 23 Oct. 2020, www.nfid.org/infectious-diseases/coronaviruses/.
5. Bert, Nina Le, et al. (2020) “SARS-CoV-2-Specific T Cell Immunity in Cases of COVID-19 and SARS, and Uninfected Controls.” Nature News, Nature Publishing Group, www.nature.com/articles/s41586-020-2550-z.