title: Human erythrocytes selectively bind and enrich infectious HIV-1 virions.
abstract: 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% of the added p24, 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.
authors.affiliation: Division of Retrovirology, United States Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, Maryland, United States of America.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Beck
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Brown
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Peachman
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
mesh_terms: D000327:Adsorption; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000821:virology; D004912:Erythrocytes / Q000378:metabolism* / Q000821:virology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007937:Leukapheresis; D007962:Leukocytes / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization