tetano
Editor, Senior Moderator
Biochimie
. 2021 Nov 15;S0300-9084(21)00259-5.
doi: 10.1016/j.biochi.2021.11.005. Online ahead of print.
SARS-CoV-2 may affect the immune response via direct inhibition of T cell receptor: Mechanistic hypothesis and rationale
Alexander B Sigalov[SUP] 1 [/SUP]
Affiliations
Abstract
During co-evolution with their hosts, many viruses have evolved a membrane fusion mechanism to facilitate host cell entry. Examples are human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2). These viruses can also infect immune cells (e.g., T cells), providing one of the possible mechanisms for the T cell lymphopenia observed in patients with these infections. Previously, we hypothesized and confirmed in vivo that like HIV-1, SARS-CoV-1 can use its fusion domain not only to enter the T cell but also to directly inhibit T cell receptor signaling. Here, based on the analysis of available structural and clinical data, we hypothesize that SARS-CoV-2 may use a similar "disarm the alarm" strategy to suppress immune responses. We also discuss the implications of this hypothesis for better understanding coronavirus disease 2019 (COVID-19) pathology, developing effective COVID-19 vaccines and improving clinical outcomes for COVID-19 patients.
Keywords: COVID-19; COVID-19 drugs; COVID-19 vaccines; Lymphopenia; SARS-CoV-2; Spike protein; T cell immune responses; T cell receptor.
. 2021 Nov 15;S0300-9084(21)00259-5.
doi: 10.1016/j.biochi.2021.11.005. Online ahead of print.
SARS-CoV-2 may affect the immune response via direct inhibition of T cell receptor: Mechanistic hypothesis and rationale
Alexander B Sigalov[SUP] 1 [/SUP]
Affiliations
- PMID: 34793886
- DOI: 10.1016/j.biochi.2021.11.005
Abstract
During co-evolution with their hosts, many viruses have evolved a membrane fusion mechanism to facilitate host cell entry. Examples are human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2). These viruses can also infect immune cells (e.g., T cells), providing one of the possible mechanisms for the T cell lymphopenia observed in patients with these infections. Previously, we hypothesized and confirmed in vivo that like HIV-1, SARS-CoV-1 can use its fusion domain not only to enter the T cell but also to directly inhibit T cell receptor signaling. Here, based on the analysis of available structural and clinical data, we hypothesize that SARS-CoV-2 may use a similar "disarm the alarm" strategy to suppress immune responses. We also discuss the implications of this hypothesis for better understanding coronavirus disease 2019 (COVID-19) pathology, developing effective COVID-19 vaccines and improving clinical outcomes for COVID-19 patients.
Keywords: COVID-19; COVID-19 drugs; COVID-19 vaccines; Lymphopenia; SARS-CoV-2; Spike protein; T cell immune responses; T cell receptor.