SARS-COV-2 Uses CD4 to infect T Helper Lymphocytes

ABSTRACT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2) is the agent of a major global outbreak of respiratory tract disease known as COVID-19. CoV-2 infects the lungs and may cause several immune-related complications such as lymphocytopenia and cytokine storm which are associated with the severity of the disease and predict mortality. The mechanism by which CoV-2 infection may result in immune system dysfunction is not fully understood. Here we showed that CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells. CoV-2 is found in the blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that CoV-2 spike glycoprotein (S) (sCoV-2) directly binds to the CD4 co-receptor, which in turn mediates the entry of CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2. Once inside T helper cells, CoV-2 assembles viral factories, impairs cell function and may cause cell death. CoV-2 infected T helper cells express higher amounts of IL-10, which has been associated with viral persistence and disease severity. Thus, CD4-mediated CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID-19 patients.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): T Cell, Blood

DISEASE(S): Covid-19

SUBMITTER: Victor Corasolla Carregari  

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD020967 | Pride | 2023-07-28

REPOSITORIES: Pride