CD71 ⁺ Erythroid Cells Exacerbate HIV-1 Susceptibility, Mediate trans -Infection, and Harbor Infective Viral Particles

Abstract

Immature red blood cells (erythroid precursors or CD71+ erythroid cells) have a wide range of immunomodulatory properties. In this study, we found that these erythroid precursors are abundant in the human cord blood/placental tissues, in the blood of HIV-infected and anemic individuals. We observed that these cells exacerbate HIV-1 replication/infection in target cells and even make HIV target cells more permissible to HIV infection. In addition, we found that HIV gets a free ride by binding on the surface of these cells and thus can travel to different parts of the body. In agreement, we noticed a positive correlation between the plasma viral load and the frequency of these cells in HIV patients. More importantly, we observed that infective HIV particles reside inside these erythroid precursors but not mature red blood cells. Therefore, these cells by harboring HIV can play an important role in HIV pathogenesis.

Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2

“…Consistent with previous reports in the context of infection (e.g. HIV) and cancer 26,29,31 , CECs from COVID-19 patients exhibited substantial expression of arginase II and ROS. In addition, arginase I expression has not previously been reported in CECs.…”

“…1F and 1G) and ROS ( Fig. 1H and 1I) compared to other immune cell lineages, similar to what has been described for their counterparts in HIV 31 and cancer 29 . For the very first time, we also detected expression of arginase I in CECs of COVID-19 patients ( Fig.…”

“…Although the lack of organelles in RBCs precludes viral survival/replication, this might not be true for CECs. Recently, we reported that HIV can reside and possibly replicate within CECs 31 .…”

“…We and others have reported that CECs compromise innate and adaptive immune responses against infections and tumors due to their immunosuppressive properties 24,[26][27][28][29][30] . In addition, it has been shown that CECs can harbor infective HIV particles and the binding of HIV to CD235a mediates HIV trans-infection to CD4 + T cells 31 . However, whether these cells can be the target of SARS-CoV-2 remains to be explored.…”

Do Blood Group Antigens and the Red Cell Membrane Influence Human Immunodeficiency Virus Infection?

“…Others have gone on to reveal that in the absence of antibodies and complement, cell-free HIV was still capable of binding to red cells and, consequently, it was concluded that red cells, like dendritic cells, could act as a viral reservoir prior to the invasion of CD4+ cells [4]. Recently, further research has established that circulating immature CD71+ erythrocytes in HIV+ individuals are host to both intracellular and surface HIV particles, which significantly increases the movement, infectivity and replication of the virus [5]. These reports have all raised questions around the exact mechanism of HIV attachment and whether blood group antigens influence susceptibility.…”