Human Rhinovirus Type 2-Antibody Complexes Enter and Infect Cells via Fc-γ Receptor IIB1

Abstract

HeLa cells were stably transfected with a cDNA clone encoding the B1 isoform of the mouse Fc␥RII receptor (hereafter referred to as HeLa-FcRII cells). The receptor was expressed at high level at the plasma membrane in about 90% of the cells. These cells bound and internalized mouse monoclonal virus-neutralizing antibodies 8F5 and 3B10 of the subtype immunoglobulin G2a (IgG2a) and IgG1, respectively. Binding of the minor-group human rhinovirus type 2 (HRV2) to its natural receptors, members of the low-density lipoprotein receptor family, is dependent on the presence of Ca 2؉ ions. Thus, chelating Ca 2؉ ions with EDTA prevented HRV2 binding, entry, and infection. However, upon complex formation of 35 S-labeled HRV2 with 8F5 or 3B10, virus was bound, internalized, and degraded in HeLa-FcRII cells. Furthermore, challenge of these cells with HRV2-8F5 or HRV2-3B10 complexes resulted in de novo synthesis of viral proteins, as shown by indirect immunofluorescence microscopy. These data demonstrate that minor-group receptors can be replaced by surrogate receptors to mediate HRV2 cell entry, delivery into endosomal compartments, and productive uncoating. Consequently, the conformational change and uncoating of HRV2 appears to be solely triggered by the low-pH (pH < 5.6) environment in these compartments.

Neutralized Adenovirus-Immune Complexes Can Mediate Effective Gene Transfer via an Fc Receptor-Dependent Infection Pathway

“…The effect of antibodies reported here confirms previous reports of antibodyenhanced infection in a number of viruses, including human immunodeficiency virus (HIV), coxsackie virus B4, and rhinovirus (6,24,25,69). Unlike the observations reported here, antibody-enhanced infection by viruses that are tropic for Fc␥R-bearing cells did not constitute a change in the tropism of the virus.…”

Uncoating of human rhinoviruses

“…(1) The avidity increases roughly exponentially with the number of receptor modules within the molecule [117,118], (2) The virus is stabilised by receptor binding presumably via impeding structural changes [124], (3) This stabilisation is overcome by competition with the b-propeller domain of these receptors at low pH [125,126] that also facilitates virus release [111]. As shown by the use of the V-ATPase inhibitor bafilomycin A1, minor group HRVs are strictly dependent on low endosomal pH for infection [6,97,109,110,112,[127][128][129][130][131].…”

Opening of Size-Selective Pores in Endosomes during Human Rhinovirus Serotype 2 In Vivo Uncoating Monitored by Single-Organelle Flow Analysis

“…Major-group HRVs bind ICAM-1, which resembles the poliovirus receptor in that it belongs to the immunoglobulin superfamily and catalyzes uncoating (43). Minor-group HRVs, such as HRV2, bind members of the low-density lipoprotein receptor family (15), which mediate internalization but do not catalyze uncoating (2,5). Minor-group HRVs are thus absolutely dependent on the low endosomal pH for infection to occur.…”