Albumin Enhances the Rate at Which Coxsackievirus B3 Strain 28 Converts to A-Particles

Abstract

Three strains of coxsackievirus B3 (CVB3) differ by single mutations in capsid protein VP1 or VP3 and also differ in stability at 37°C in tissue culture medium. Among these strains, the CVB3/28 parent strain has been found to be uniquely sensitive to a component in fetal bovine serum (FBS) identified as serum albumin. In cell culture medium, serum increased the rate of CVB3/28 conversion to noninfectious particles at least 2-fold. The effect showed a saturable dose response. Rates of conversion to noninfectious virus with high concentrations of soluble coxsackievirus and adenovirus receptor (sCAR) were similar with and without FBS, but FBS amplified the catalytic effect of 100 nM sCAR nearly 3-fold. Such effects in other systems are due to nonessential activating cofactors. IMPORTANCE A factor other than the virus receptor expressed by target cells has been found to accelerate the loss of an enterovirus (CVB3/28) infectious titer, with little effect on nearly identical mutant strains. The destabilizing factor in fetal bovine serum, identified as albumin, does not interfere with the catalytic activity of soluble receptor at saturating receptor concentrations and amplifies the catalytic activity of the soluble receptor at a concentration that otherwise produces about one-third the saturated receptor-catalyzed rate of virus decay. This finding evidences the possibility that other virus-“priming” ligands may also be nonessential activating cofactors that serve to accelerate receptor-catalyzed viral eclipse.

Structural Studies Reveal that Endosomal Cations Promote Formation of Infectious Coxsackievirus A9 A-Particles, Facilitating RNA and VP4 Release

“…In enteroviruses E1 and E12 and coxsackievirus B3, serum albumin promotes virion expansion in a dose-dependent manner by sequestering the lipid factor from the VP1 hydrophobic pocket, as shown in in vitro experiments ( 6 , 20 , 21 ). Here, we studied and compared the roles of serum albumin and endosomal ion concentrations at neutral pH in triggering CVA9 expansion and genome release.…”

“…Despite extensive research, the physiological triggers leading to enterovirus uncoating after internalization, other than receptor binding and low pH in the endosomes, are poorly understood ( 19 ). Some studies have reported serum albumin as an uncoating cue for E1, E12, and coxsackievirus B3 ( 6 , 20 , 21 ).…”

Specific bacterial cell wall components influence the stability of Coxsackievirus B3

“…(A) CVB3 decay at 37°C when incubated with DMEM (slope= −0.06651; R2= 0.6940) or 10 8 of S. enterica (slope= 0.001960; R2= 0.9337). The first-order decay rate for CVB3 was determined by a best-fit line generated by fitted linear regression as previously described (48). (B) Rates of CVB3 Decay in either PBS or 10 8 CFUs of S. enterica .…”

Structural studies reveal that endosomal cations promote formation of infectious CVA9 A particles, facilitating RNA and VP4 release

“…In enteroviruses E1, E12 and coxsackievirus B3 serum albumin promotes virion expansion in a dosedependent manner by sequestering the lipid factor from the VP1 hydrophobic pocket as shown in in vitro experiments (6,20,21). Here we studied and compared the roles of serum albumin and endosomal ion concentrations at neutral pH in triggering CVA9 expansion and genome release.…”

“…Despite extensive research, the physiological triggers leading to enterovirus uncoating after internalization, other than receptor binding and low pH in the endosomes, are poorly understood (19). Some reports show serum albumin as an uncoating cue for E1, E12 and coxsackievirus B3 (6, 20, 21).…”