Among the various viral diseases, two of the most prevalent viruses that have affected millions of lives are severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and human immunodeficiency virus-1 (HIV-1). The current coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has infected more than 319 million individuals and claimed more than 5.52 million lives worldwide. According to a recent report by the Joint United Nations Program on HIV / AIDS (UNAIDS), more than 38 million speople live with HIV-1 (PLWH), and over 36 million AIDS-related deaths have occurred since the beginning of the AIDS epidemic.
Study: A single-cell atlas reveals common and diverse immune responses and metabolism during SARS-CoV-2 and HIV-1 infections. Image credit: Design_Cells / Shutterstock
SARS-CoV-2 and HIV-1
Studies have shown that both SARS-CoV-2 and HIV-1 are RNA viruses and have higher mutation rates than DNA viruses. Although both viruses have been characterized as highly virulent, the mode of disease progression differs significantly. For example, in the case of SARS-CoV-2, mortality and morbidity may be observed within a few days after infection, whereas for HIV-1 infection it takes months or years. Also in SARS-CoV-2 infection, neutralizing antibodies are generated soon after infection, but with PLWH it takes many years to develop antibodies.
Researchers have reported that PLWHs with compromised immune systems make them susceptible to SARS-CoV-2 infection. In addition, this group has shown suboptimal responses to SARS-CoV-2 vaccination. Therefore, complete immune profiling of SARS-CoV-2 and HIV-1 infections would elucidate the mechanism of disease progression that could guide researchers in the discovery of new therapeutic agents.
Many COVID-19 patients with severe infection produce high levels of inflammatory cytokines and chemokines, such as IL-6, IL-10, TNF-α, IFN-γ and IP-10. Similarly, these cytokines are also released during acute HIV-1 infection and may continue if left untreated. Different types of immune cells drive inflammatory reactions during viral infection.
The distribution and cell type-specific functions of different immune cells, such as T cells, B cells, macrophages, natural killer cells, dendritic cells, monocytes, are different across different infections, stages of disease progression, and conditions.
Single cell RNA sequencing method
Single cell RNA sequencing (scRNA-seq) has been widely used to understand heterogeneity within subgroups of immune cells. This sequencing method provides very accurate annotations of individual cells. It has become a powerful tool for elucidating complex cell-cell interactions and understanding the subpopulation dynamics of single-cell resolution.
Researchers have indicated that there is not much evidence available regarding immune cell populations during HIV-1 and COVID-19 infections at single cell level. Although several scRNA seq atlases have been developed on COVID-19, they differ significantly in granularity and markers used for annotation. There are not many HIV-1 scRNA-seq profiling studies available comparable to COVID-19 infection.
A new study
A new study, posted to bioRxiv* preprint server, has developed a single-cell atlas that presents the common and distinct immune responses and metabolism following SARS-CoV-2 and HIV-1 infections.
Researchers from the University of Chicago and Northwestern University used single-cell transcriptomics to systematically compare scRNA seq data for 115,272 single Peripheral Blood Mononuclear Cells (PBMCs) obtained from seven COVID-19, nine HIV-1 and three healthy patients. In doing so, they produced a high-quality unified cellular atlas of the immune landscape by combining the benefits of all three methods of annotating scRNA seq data, which include molecular-profile correlation-based label transfer, manual annotation, and deep-learning-based classification.
The newly developed atlas enabled researchers to compare the phenotypic features and regulatory pathways of the major immune cells. They reported common signatures of inflammation, i.e. IFN-I and cytokine-mediated signaling, as well as faulty mitochondrial function in both COVID-19 and HIV-1. However, the difference between COVID-19 and HIV-1 was found in terms of antibody diversity, cell signaling, IFN-I signaling, and metabolic function. For example, cytokine response to IL-2, IL-4, and IL-20 signaling was found to be more prominent in COVID-19 patients compared to HIV-1 patients who exhibited high levels of NF-κB signaling.
Researchers identified 27 different cell types, including five B cell subgroups, two dendritic cell subgroups, four monocyte subgroups, seven CD4 + T cell subgroups, eight CD8 + T cell subgroups, and a natural killer cell subgroup, post-COVID-19 and HIV-1 infections. However, the types and frequencies of cellular communication among immune cells differed significantly between COVID-19 and HIV-1 patients. The authors reported the development of inhibitory interactions mediated by CTLA4 and HAVCR2 that were characteristic of COVID-19 patients. Consistent with previous reports, a robust humoral immune response was found in both COVID-19 and HIV-1 patients. In addition, IFN-I signaling has been reported to be closely associated with both HIV-1 and COVID-19 infection, promoting essential cellular functions such as cell signaling, motility, and cytokine secretion. The authors reported a decrease in mitochondrial oxidative phosphorylation (OXPHOS) and ribosombiogenesis in response to both SARS-CoV-2 and HIV-1 infection.
The current study has offered an important resource for understanding the pathophysiological differences between COVID-19 and HIV-1. It revealed that the HIV-1 antibody repertoire was much less diverse compared to the COVID-19 antibody repertoire. One of the benefits of repertoire mapping is that it helps researchers locate high-frequency and overlapping combinations in sequences that could inspire antibody-based therapy to treat comorbid patients. The authors are optimistic that this study will help develop new molecular targets for the treatment of these diseases.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered essential, guide clinical practice / health-related behavior or be treated as established information.