Attenuated live vaccine usage affects accurate measures of virus diversity and mutation rates in avian coronavirus infectious bronchitis virus

Abstract

The full-length genomes of 11 infectious bronchitis virus (IBV) field isolates from three different types of the virus; Massachusetts (Mass), Connecticut (Conn) and California (CAL) isolated over a 41, 25 and 8 year period respectively, were sequenced and analyzed to determine the mutation rates and level of polymorphisms across the genome. Positive selection was not detected and mutation rates ranged from 10(-4) to 10(-6)substitutions/site/year for Mass and Conn IBV types where attenuated live vaccines are routinely used to control the disease. In contrast, for CAL type viruses, for which no vaccine exists, positive selection was detected and mutation rates were 10 fold higher ranging from 10(-2) to 10(-3)substitutions/site/year. Lower levels of genetic diversity among the Mass and Conn viruses as well as sequence similarities with vaccine virus genomes suggest that the origin of the Mass and all but one of the Conn viruses was likely vaccine virus that had been circulating in the field for an unknown but apparently short period of time. The genetic data also identified a recombinant IBV isolate with 7 breakpoints distributed across the entire genome suggesting that viruses within the same serotype can have a high degree of genetic variability outside of the spike gene. These data are important because inaccurate measures of genetic diversity and mutation rates could lead to underestimates of the ability of IBV to change and potentially emerge to cause disease.

Effects of chicken anaemia virus and infectious bursal disease virus-induced immunodeficiency on infectious bronchitis virus replication and genotypic drift

“…For example, the replicase proteins in open reading frame 1ab have been shown to be associated with pathogenicity (Ammayappan et al, 2009). However, the spike gene in IBV appears to be the most reliable measure of genetic change leading to the emergence of new viruses capable of causing disease (McKinley et al, 2011). Indeed, our previous results have confirmed that population analyses based on S1 genotype/phenotype allow assessment of IBV drift (Gallardo et al, 2010).…”

Genetic, antigenic, and pathogenic characteristics of avian infectious bronchitis viruses genotypically related to 793/B in China

“…The replication of coronavirus genomes, including that of IBV, requires a step in which a set of subgenomic RNAs is generated. This mechanism promotes homologous recombination events (McKinley et al, 2011). Recombination contributes to the genetic 1 4/91 vaccine NC b 0/10 c 0/10 0/10 0/10 3/10 6/10 10/10 10/10 10/10 d 10/10 10/10 10/10 10/10 10/10 2 NV ck/CH/LSD/110851 0/10 0/10 -----0/10 9/10 10/10 10/10 10/10 10/10 3 4/91 vaccine ck/CH/LSD/110851 0/10 0/10 0/10 0/10 3/10 5/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 4 NV ck/CH/LSD/110857 0/10 0/10 ------0/10 10/10 10/10 10/10 10/10 10/10 5 4/91 vaccine ck/CH/LSD/110857 0/10 0/10 0/10 0/10 3/10 5/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 6 NV e ck/CH/LHB/130575 5/10 0/10 ------0/10 8/10 10/10 10/10 10/10 10/10 7 4/91 vaccine ck/CH/LHB/130575 0/10 0/10 0/10 0/10 4/10 5/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 8 NV ck/CH/LGD/090907 10/10 2/10 ------0/10 8/8 8/8 8/8 8/8 8/8 9 4/91 vaccine ck/CH/LGD/090907 0/10 0/10 0/10 0/10 3/10 6/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10 NV ck/CH/LGD/120723 10/10 7/10 ------0/10 3/3 3/3 3/3 3/3 3/3 11 4/91 vaccine ck/CH/LGD/120723 0/10 0/10 0/10 0/10 3/10 5/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 12 NV ck/CH/LHLJ/04V 10/10 3/10 ------0/10 8/8 7/7 7/7 7/7 7/7 13 4/91 vaccine ck/CH/LHLJ/04V 0/10 0/10 0/10 0/10 2/10 6/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 14 NV ck/CH/LDL/091022 10/10 2/10 ------0/10 8/8 8/8 8/8 8/8 8/8 15 4/91 vaccine ck/CH/LDL/091022 0/10 0/10 0/10 0/10 3/10 6/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 16 NV NC 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 a Days after vaccination/challenge.…”

The avian coronavirus spike protein

“…It is, however, yet impossible to predict based on a genetic sequence whether the IBV strain is sufficiently attenuated, while potent enough to induce and effective immune response. In addition, the use of attenuated live-vaccines poses a risk of residual pathogenicity associated with vaccine backpassage in flocks (Abro et al, 2012;McKinley et al, 2011;OIE, 2013). Despite this, live attenuated IBV vaccines are still the golden standard to protect chickens from IBV, as immune responses are high.…”