Antigenic and genetic variation in influenza A (H1N1) virus isolates recovered from a persistently infected immunodeficient child

Abstract

Antigenic and genetic variations have been analyzed in eight consecutive isolates recovered from a child with severe combined immunodeficiency syndrome persistently infected with naturally acquired type A (HlNl) influenza virus over a 10-month period. Hemagglutination inhibition reactions and T1 oligonucleotide fingerprinting demonstrated that these viruses were related to strains causing outbreaks in the United States at that time (1983 to 1984) but that antigenic and genetic differences between consecutive isolates could be detected. This variation between isolates was examined further by sequencing the RNAs encoding the HAl region of the hemagglutinin (HA) and the nucleoprotein (NP) in five of the consecutive isolates. Multiple point mutations were detected in both genes, and a deletion of one amino acid was detected in the HA. Depending on the isolates compared, 5.8 x 10-3 to 17 x 10-3 substitutions per nucleotide site per year were detected in the RNAs encoding the HAl, and 3.5 x 10-3 to 24 x 10-3 substitutions per nucleotide site per year were detected in the NP gene. Fifty-four percent of the base changes in the HAl and 73% in the NP led to amino acid substitutions. A progressive accumulation of mutations over time was not observed, suggesting that the genetic diversity of these viruses may best be interpreted as the result of shifts in the population equilibrium (quasispecies) of replicating variant genomes.

Gonadal pathogenicity of an infectious bronchitis virus strain from the Massachusetts genotype

“…These changes in tissue tropism could be a consequence of escaping mechanisms of the virus associated with the immune pressures driven by vaccination protocols for IBV [39,40]. Furthermore, it has been demonstrated that immunity is not the only selective pressure on IBV [41] and the genetic diversity in viral isolates is attributed to shifts in population equilibrium of the replicating viral genomes even in the absence of immune selection pressure [42]. Such divergence between genotype and predominant pathotype or tissue tropism has also been reported in an IBV isolate from Egypt (Egypt/F/ 03), which, despite being classified as Massachusetts, showed a marked nephropathogenicity in experimentally infected SPF chickens [43].…”

Viral Quasispecies Evolution

“…When a mutant spectrum harbors an ample repository of variants, selection of genome subsets in a new environment can be very rapid. Astonishing rates of evolution of consensus sequences in vivo, of 10 Ϫ2 substitution per site per year or even higher, can be attained (87,136,311,341,473,698,753). It should be appreciated that such rates of evolution are 10 6 -to 10 7 -fold higher than the average rates estimated for cellular genes during long-term evolution (the values and implications are reviewed in references 189 and 376).…”

Long-term virus evolution in nature

“…The number of infectious particles shed by an infected host determines the probability of transmission to susceptible hosts (Section 7.2), and of producing an emergence in a new host species. Viral population numbers and the number of transmissible particles can be largely amplified in immunocompromised individuals, and have been termed super-spreaders; they can contribute large amounts of variant viruses to the transmission lottery (Rocha et al, 1991;Paunio et al, 1998;Gavrilin et al, 2000;Khetsuriani et al, 2003;Small et al, 2006;Odoom et al, 2008;Woolhouse, 2017). Concerning the recipient hosts, the higher the number of potentially susceptible hosts that come into contact with an infected donor, the higher the probability of establishment of an emergent infection.…”