Vitronectin receptor antibodies inhibit infection of HeLa and A549 cells by adenovirus type 12 but not by adenovirus type 2

Abstract

The penton base gene from adenovirus type 12 (Adl2) was sequenced and encodes a 497-residue polypeptide, 74 residues shorter than the penton base from Ad2. The Ad2 and Adl2 proteins are highly conserved at the aminoand carboxy-terminal ends but diverge radically in the central region, where 63 residues are missing from the Adl2 sequence. Conserved within this variable region is the sequence Arg-Gly-Asp (RGD), which, in the Ad2 penton base, binds to integrins in the target cell membrane, enhancing the rate or the efficiency of infection. The Adl2 penton base was expressed in Escherichia coli, and the purified refolded protein assembled in vitro with Ad2 fibers. In contrast to the Ad2 penton base, the Adl2 protein failed to cause the rounding of adherent cells or to promote attachment of HeLa S3 suspension cells; however, A549 cells did attach to surfaces coated with either protein and pretreatment of the cells with an integrin avP5 monoclonal antibody reduced attachment to background levels. Treatment of HeLa and A549 cells with integrin otvP3 or otvj35 monoclonal antibodies or with an RGD-containing fragment of the Ad2 penton base protein inhibited infection by Adl2 but had no effect on and in some cases enhanced infection by Ad2. Purified Ad2 fiber protein reduced the binding of radiolabeled Ad2 and Adl2 virions to HeLa and A549 cells nearly to background levels, but the concentrations of fiber that strongly inhibited infection by Ad2 only weakly inhibited Adl2 infection. These data suggest that atv-containing integrins alone may be sufficient to support infection by Adl2 and that this pathway is not efficiently used by Ad2.

Targeted Recombination Demonstrates that the Spike Gene of Transmissible Gastroenteritis Coronavirus Is a Determinant of Its Enteric Tropism and Virulence

“…Mean values of three independent determinations Ϯ the standard errors of the means are shown. (4,5,55,56), echoviruses (63,64), aphtoviruses (21), herpes simplex virus (72), adenovirus (1,26,70), and human immunodeficiency virus (65). Unfortunately, the wide distribution of the receptors and accessory factors, which is broader than the observed tropism of the viruses mediated by these receptors and factors, suggests that host cell restriction is also mediated by additional limiting processes that probably take place after virus binding and internalization.…”

A single gene encoding the fiber is responsible for variations in virulence in the fowl adenoviruses

“…The ability of a virus to replicate in different tissues raises questions about virus attachment and the role of the fiber protein. Various studies with the HAVs have shown that the fiber is responsible for initial attachment to the cellular receptor, which is followed by binding to cell surface integrins (43), a step mediated by a sequence in the penton base (1). The binding to integrins may be the common step in adenovirus infection (24), while the cellular receptors for the fiber may differ (5).…”

Unique physicochemical properties of human enteric Ad41 responsible for its survival and replication in the gastrointestinal tract

“…CAR mRNA is preferentially expressed in the heart, testis, prostate, and pancreas, which are not tissues targeted by enteric Ads infection. Moreover, the internalization of the majority of Ad serotypes is due to their interaction with integrins avh3 and avh5 via an RGD motif present in the virus penton base protein (Bai et al, 1994;Mathias et al, 1994;Wickham et al, 1993). However, Ad40 and Ad41 lack the RGD motif in their penton bases or fibers (Albinsson and Kidd, 1999).…”