erythrocyte-bound HIV-1 might comprise an important surface

Human erythrocytes selectively bind and enrich infectious HIV-1 virions.

Beck Z, Brown BK, Wieczorek L, Peachman KK, Matyas GR, Polonis VR, Rao M, Alving CR. PLoS One.2009.4:e8297.

Although CD4(+) cells represent the major target for HIV infection in blood, claims of complement-independent binding of HIV-1 to erythrocytes and the possible role of Duffy blood group antigen, have generated controversy . To examine the question of binding to erythrocytes, HIV-1 was incubated in vitro with erythrocytes from 30 healthy leukapheresis donors, and binding was determined by p24 analysis and adsorption of HIV-1 with reduction of infectivity for CD4(+) target cells. All of the cells, regardless of blood group type, bound HIV-1 p24. A typical preparation of erythrocytes bound <2.4%>, but erythrocytes selectively removed essentially all of the viral infectivity as determined by decreased infection of CD4(+) target cells; however, cell-associated HIV-1 was approximately 100-fold more efficient, via trans infection, than unadsorbed virus for infection of CD4(+) cells. All of the bound HIV-1 p24 was released by treatment of the cells with EDTA, and binding was optimized by adding Ca(2+) and Mg(2+) during the washing of erythrocytes containing bound HIV-1. Although the small number of contaminating leukocytes in the erythrocyte preparation also bound HIV-1 p24, there was no significant binding to CD4, and it thus appears that the binding occurred on leukocytes at non-CD4 sites. Furthermore, binding occurred to erythrocyte ghosts from which contaminating leukocytes had been previously removed. The results demonstrate that erythrocytes incubated in vitro with HIV-1 differentially adsorb all of the infectious HIV-1 virions (as opposed to non-infectious or degraded virions) in the absence of complement and independent of blood group, and binding is dependent on divalent cations. By analogy with HIV-1 bound to DC-SIGN on dendritic cells, erythrocyte-bound HIV-1 might comprise an important surface reservoir for trans-infection of permissive cells.

the exact mechanism of binding of HIV-1 to erythrocytes remains unknown, there is likely more than one mechanism. This study demonstrates that in the absence of complement which HIV-1 usually activates so that it can bind to complement receptors on cells, HIV-1 binds to erythrocytes, regardless of whether they display Duffy blood group antigen or not. The binding occurs only on the cell surface, permitting erythrocytes with HIV-1 on their surface to present it to CD4+ cells which are not in plentiful supply compared to other cell types. Thus, erythrocytes in the blood may be acting like dendritic cells in tissue to carry and offer HIV-1 to the very target cells that HIV-1 uses for replication, in a process called trans infection. This appears likely to be a far more frequent infecting mechanism than direct infection of CD4+ cells by circulating free virus.