Contrasting mechanistic susceptibilities of hematopoietic and endothelial stem-progenitor cells in respective pathogeneses of HIV-1 and SARS-CoV-2 infections

Abstract

The multitude of cellular types can be expected to behave differently when receiving invading pathogens such as mammalian viruses. The nature-dictated causes for such intrinsic cellular diversity become the criteria for the emergence of specific virus-receptor interactions on that particular host cellular surface, in order to accommodate contact with various other living entities whether desirable to the host or not. At present, we are presented with an example of two contrasting behaviours wherein the well-known HIV-1 and the more recently emergent SARS-CoV-2 cause adverse consequences to the differentiation and functions of progenitor stem cells. These include the two different downstream multipotent CD34+ hematopoietic (HSPC) and CD133+ endothelial (ESPC) stem-progenitor cells of their common pluripotent hemangioblast precursors. The two viruses target the respective endothelial and hematopoietic stem-progenitor cells to thrive upon the relevant host cellular surrounded stromal microenvironments by adopting reciprocally-driven mechanistic routes, which incidentally cause pathogenesis either directly of ESPC (SARS-CoV-2), or indirectly of HSPC (HIV-1). HIV-1 utilizes the CD4+ T-lymphocyte receptor thereby advancing pathogenesis indirectly to the CD34+ HSPC. SARS-CoV-2 directly targets the CD133+ ESPC via ACE2 receptor causing cytokine storms of the CD4+ T-lymphocytes. In this manner, these two viruses cause and extend their damage to the other cellular sub/types coexisting in the host cellular microenvironments. The infected individuals require clinical interventions that are efficacious to prevent cellular dysfunction and ultimate cell depletion or death. We infer from these viruses mediated pathogeneses mechanisms a potential common origin of microRNA molecular therapies to address cellular dysfunctions and prevent cell loss.

MicroRNA target homeobox messenger RNA in HIV induced hematopoietic inhibition

“…Thus, our observations were the first reported findings linking HIV-1 infection to dynamic differential regulation of specific miRNAs, which in turn inhibit hematopoiesis to cause virus-induced hematological disorders in infected patients with HIV/AIDS ( Padmanabhan et al, 2020 ). Homeobox gene-encoded transcriptomes are expected to play an important role in the onset of cytopenias ( Koka and Ramdass, 2023 ). Furthermore, herein we show that ( Figure 2 ) HIV-1 infection caused changes in microRNA that disrupt homeobox HOXB3 versus control GAPDH messenger RNA ( Zhou et al, 2001 ) , with the consequences of inhibiting hematopoiesis due to the loss of HOXB3 messenger RNA expression ( Figure 2 ) ( Sauvageau et al, 1997 ).…”

“…These CD34 + HSPCs’ fate changes result in altered terminally differentiated lineages of the multipotent HSPCs. Based on our published results ( Padmanabhan et al, 2020 ), we hypothesize that upon HIV-1 infection of the CD4 + thymocytes, the observed differential regulation of miR-15a and miR-24 that occurs causes abnormal post-transcriptional regulation of specific HOX gene-encoded transcriptomes ( Koka and Ramdass, 2023 ). Loss or abnormal translational entities, in turn, affect specific MAPK signaling and CD34 + cell fate, causing the dysregulation of hematopoiesis.…”