tetano
Editor, Senior Moderator
Virus Res
. 2024 Apr 18:199375.
doi: 10.1016/j.virusres.2024.199375. Online ahead of print. SARS-CoV-2 Superinfection in CD14[SUP]+[/SUP] Monocytes with Latent Human Cytomegalovirus (HCMV) Promotes Inflammatory Cascade
Shannon Harger Payen[SUP] 1 [/SUP], Kabita Adhikari[SUP] 1 [/SUP], Juli Petereit[SUP] 2 [/SUP], Timsy Uppal[SUP] 1 [/SUP], Cyprian C Rossetto[SUP] 1 [/SUP], Subhash C Verma[SUP] 3 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has posed significant challenges to global health. While much attention has been directed towards understanding the primary mechanisms of SARS-CoV-2 infection, emerging evidence suggests co-infections or superinfections with other viruses may contribute to increased morbidity and mortality, particularly in severe cases of COVID-19. Among viruses that have been reported in patients with SARS-CoV-2, seropositivity for Human cytomegalovirus (HCMV) is associated with increased COVID-19 risk and hospitalization. HCMV is a ubiquitous beta-herpesvirus with a seroprevalence of 60-90% worldwide and one of the leading causes of mortality in immunocompromised individuals. The primary sites of latency for HCMV include CD14[SUP]+[/SUP] monocytes and CD34[SUP]+[/SUP] hematopoietic cells. In this study, we sought to investigate SARS-CoV-2 infection of CD14[SUP]+[/SUP] monocytes latently infected with HCMV. We demonstrate that CD14[SUP]+[/SUP] cells are susceptible and permissive to SARS-CoV-2 infection and detect subgenomic transcripts indicative of replication. To further investigate the molecular changes triggered by SARS-CoV-2 infection in HCMV-latent CD14[SUP]+[/SUP] monocytes, we conducted RNA sequencing coupled with bioinformatic differential gene analysis. The results revealed significant differences in cytokine-cytokine receptor interactions and inflammatory pathways in cells superinfected with replication-competent SARS-CoV-2 compared to the heat-inactivated and mock controls. Notably, there was a significant upregulation in transcripts associated with pro-inflammatory response factors and a decrease in anti-inflammatory factors. Taken together, these findings provide a basis for the heightened inflammatory response, offering potential avenues for targeted therapeutic interventions among HCMV-infected severe cases of COVID-19. SUMMARY: COVID-19 patients infected with secondary viruses have been associated with a higher prevalence of severe symptoms. Individuals seropositive for human cytomegalovirus (HCMV) infection are at an increased risk for severe COVID-19 disease and hospitalization. HCMV reactivation has been reported in severe COVID-19 cases with respiratory failure and could be the result of co-infection with SARS-CoV-2 and HCMV. In a cell culture model of superinfection, HCMV has previously been shown to increase infection of SARS-CoV-2 of epithelial cells by upregulating the human angiotensin-converting enzyme-2 (ACE2) receptor. In this study, we utilize CD14[SUP]+[/SUP] monocytes, a major cell type that harbors latent HCMV, to investigate co-infection of SARS-CoV-2 and HCMV. This study is a first step toward understanding the mechanism that may facilitate increased COVID-19 disease severity in patients infected with SARS-CoV-2 and HCMV.
Keywords: Human cytomegalovirus (HCMV); coinfection; inflammation; inflammatory response; severe acute respiratory syndrome (SARS-CoV-2).
. 2024 Apr 18:199375.
doi: 10.1016/j.virusres.2024.199375. Online ahead of print. SARS-CoV-2 Superinfection in CD14[SUP]+[/SUP] Monocytes with Latent Human Cytomegalovirus (HCMV) Promotes Inflammatory Cascade
Shannon Harger Payen[SUP] 1 [/SUP], Kabita Adhikari[SUP] 1 [/SUP], Juli Petereit[SUP] 2 [/SUP], Timsy Uppal[SUP] 1 [/SUP], Cyprian C Rossetto[SUP] 1 [/SUP], Subhash C Verma[SUP] 3 [/SUP]
Affiliations
- PMID: 38642618
- DOI: 10.1016/j.virusres.2024.199375
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has posed significant challenges to global health. While much attention has been directed towards understanding the primary mechanisms of SARS-CoV-2 infection, emerging evidence suggests co-infections or superinfections with other viruses may contribute to increased morbidity and mortality, particularly in severe cases of COVID-19. Among viruses that have been reported in patients with SARS-CoV-2, seropositivity for Human cytomegalovirus (HCMV) is associated with increased COVID-19 risk and hospitalization. HCMV is a ubiquitous beta-herpesvirus with a seroprevalence of 60-90% worldwide and one of the leading causes of mortality in immunocompromised individuals. The primary sites of latency for HCMV include CD14[SUP]+[/SUP] monocytes and CD34[SUP]+[/SUP] hematopoietic cells. In this study, we sought to investigate SARS-CoV-2 infection of CD14[SUP]+[/SUP] monocytes latently infected with HCMV. We demonstrate that CD14[SUP]+[/SUP] cells are susceptible and permissive to SARS-CoV-2 infection and detect subgenomic transcripts indicative of replication. To further investigate the molecular changes triggered by SARS-CoV-2 infection in HCMV-latent CD14[SUP]+[/SUP] monocytes, we conducted RNA sequencing coupled with bioinformatic differential gene analysis. The results revealed significant differences in cytokine-cytokine receptor interactions and inflammatory pathways in cells superinfected with replication-competent SARS-CoV-2 compared to the heat-inactivated and mock controls. Notably, there was a significant upregulation in transcripts associated with pro-inflammatory response factors and a decrease in anti-inflammatory factors. Taken together, these findings provide a basis for the heightened inflammatory response, offering potential avenues for targeted therapeutic interventions among HCMV-infected severe cases of COVID-19. SUMMARY: COVID-19 patients infected with secondary viruses have been associated with a higher prevalence of severe symptoms. Individuals seropositive for human cytomegalovirus (HCMV) infection are at an increased risk for severe COVID-19 disease and hospitalization. HCMV reactivation has been reported in severe COVID-19 cases with respiratory failure and could be the result of co-infection with SARS-CoV-2 and HCMV. In a cell culture model of superinfection, HCMV has previously been shown to increase infection of SARS-CoV-2 of epithelial cells by upregulating the human angiotensin-converting enzyme-2 (ACE2) receptor. In this study, we utilize CD14[SUP]+[/SUP] monocytes, a major cell type that harbors latent HCMV, to investigate co-infection of SARS-CoV-2 and HCMV. This study is a first step toward understanding the mechanism that may facilitate increased COVID-19 disease severity in patients infected with SARS-CoV-2 and HCMV.
Keywords: Human cytomegalovirus (HCMV); coinfection; inflammation; inflammatory response; severe acute respiratory syndrome (SARS-CoV-2).