Abstract
The integrins function as the primary receptor molecules for the pathogenic infection of foot-and-mouth disease virus (FMDV) in vivo, while the acquisition of a high affinity for heparan sulfate (HS) of some FMDV variants could be privileged to facilitate viral infection and expanded cell tropism in vitro. Here, we noted that a BHK-adapted Cathay topotype derivative (O/HN/CHA/93tc) but not its genetically engineered virus (rHN), was able to infect HS-positive CHO-K1 cells and mutant pgsD-677 cells. There were one or three residue changes in the capsid proteins of O/HN/CHA/93tc and rHN, as compared with that of their tissue-originated isolate (O/HN/CHA/93wt). The phenotypic properties of a set of site-directed mutants of rHN revealed that E83K of VP1 surrounding the fivefold symmetry axis was necessary for the integrin-independent infection of O/HN/CHA/93tc. L80 in VP2 was essential for the occurrence of E83K in VP1 during the adaptation of O/HN/CHA/93wt to BHK-21 cells. L80M in VP2 and D138G in VP1 of rHN was deleterious, which could be compensated by K83R of VP1 for restoring an efficient infection of integrin-negative CHO cell lines. These might have important implications for understanding the molecular and evolutionary mechanisms of the recognition and binding of FMDV with alternative cellular receptors.
Highlights
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious vesicular disease in domestic and wild cloven-hoofed animals, mostly cattle, swine, sheep and goats, and many species of ruminants [1,2]
E83K in VP1 is Responsible for the Alteration in Cellular Receptor Recognition of O/HN/CHA/93tc to Establish an Efficient Infection in Integrin-Negative CHO Cell Lines
As a matter of fact, rHNK1083R and rHNM2080L+G1138D were extensively colocalized with caveolin, but there was slight colocalization of clathrin in heparan sulfate (HS)-positive CHO-K1 cells and mutant pgsD-677 cells (Figure 5). These results offered an insight into the internalization of a cell-adapted Cathay topotype virus and its genetically engineered foot-and-mouth disease virus (FMDV) variants with a high affinity for heparin and non-RGD binding capacity, for the infection of cultured cells
Summary
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious vesicular disease in domestic and wild cloven-hoofed animals, mostly cattle, swine, sheep and goats, and many species of ruminants [1,2]. The virus is the prototypic member that belongs to the genus Aphthovirus of the Picornaviridae family (http://ictv.global/report/). The viral genome is a positive-sense, single-stranded RNA approximately 8500 nucleotides in length. The FMDV RNA consists of a single. There is a small viral protein (termed VPg or 3B) covalently linked to the 50 terminus of the genomic RNA [5]. The ORF of FMDV encodes a precursor polyprotein that is subsequently cleaved into four structural proteins (VP1–4) and several non-structural proteins (Lpro, 2A, 2B, 2C, 3A, 3B1–3 , 3Cpro, 3Dpol) [6]. The nonenveloped FMDV virion is assembled from 60 copies each of three surface-exposed capsid proteins VP1–3 and an internal polypeptide VP4, with icosahedral symmetry in a diameter of 27–30 nm [7]
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