Genetic reassortment of avian, swine, and human influenza A viruses in American pigs

Abstract

In late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of North Carolina, Texas, Minnesota, and Iowa. Four viral isolates from outbreaks in different states were analyzed genetically. Genotyping and phylogenetic analyses demonstrated that the four swine viruses had emerged through two different pathways. The North Carolina isolate is the product of genetic reassortment between H3N2 human and classic swine H1N1 influenza viruses, while the others arose from reassortment of human H3N2, classic swine H1N1, and avian viral genes. The hemagglutinin genes of the four isolates were all derived from the human H3N2 virus circulating in 1995. It remains to be determined if either of these recently emerged viruses will become established in the pigs in North America and whether they will become an economic burden.

FIG. 1

Phylogenetic tree of HA1 nucleotide sequences of the H3 hemagglutinin. The tree was generated by the maximum parsimony method in the PAUPsearch and PAUPdisplay programs of the Wisconsin Package version 9.1-Unix (Genetics Computer Group) and is rooted to the H4 sequence of A/Duck/Czechoslovakia/56 (H4N6). Horizontal lines are proportional to the numbers of nucleotide substitutions between branch points. Swine viruses are underlined, and the SW98 viruses are boxed. Abbreviations: DKUKR63, A/Duck/Ukraine/1/63 (H3N8); DKHOK77, A/Duck/Hokkaido/5/77 (H3N?); AICH68, A/Aichi/2/68 (H3N2); MEM72, A/Memphis/102/72 (H3N2); PCH73, A/Port Chalmers/1/73 (H3N2); VIC75, A/Victoria/3/75 (H3N2); ENG77, A/England/321/77 (H3N2); BANGK79, A/Bangkok/1/79 (H3N2); MEM86, A/Memphis/6/86 (H3N2); SING89, A/Singapore/12/89 (H3N2); BEI92, A/Beijing/32/92 (H3N2); NAN93, A/Nanchang/12/93 (H3N2); NAN95, A/Nanchang/933/95 (H3N2); FIN363-95, A/Finland/363/95 (H3N2); FIN339-95, A/Finland/339/95 (H3N2); ID95, A/Idaho/4/95 (H3N2); SHIG97, A/Shiga/25/97 (H3N2); SYD97, A/Sydney/05/97 (H3N2); SWHK1-76, A/Swine/Hong Kong/1/76 (H3N2); SWHK3-76, A/Swine/Hong Kong/3/76 (H3N2); SWCOL77, A/Swine/Colorado/1/77 (H3N2); SWHK82-78, A/Swine/Hong Kong/82/78 (H3N2); SWHK127-78, A/Swine/Hong Kong/127/78 (H3N2); SWITY83, A/Swine/Italy/309/83 (H3N2); SWUKK84, A/Swine/Ukkel/1/84 (H3N2); SWUTR85, A/Swine/Utrecht/4/85 (H3N2); SWITY87, A/Swine/Italy/635/87 (H3N2); SWAG90, A/Swine/Ange-Gardien/150/90 (H3N2); SWNET91, A/Swine/Netherlands/784/91 (H3N2); SWNET93, A/Swine/Netherlands/L2/93 (H3N2); SWOBI93, A/Swine/Obihiro/1/93 (H3N2); SWOBI94, A/Swine/Obihiro/1/94 (H3N2); SWBEL94, A/Swine/Belgium/231/94 (H3N2); SWOED96, A/Swine/Oedenrode/7C/96 (H3N2); SWBRE97, A/Swine/Breugel/97 (H3N2).

FIG. 2

Phylogenetic trees for partial PB2 and NP sequences of influenza A viruses. Nucleotide residues 44 to 1,600 of all PB2 genes and residues 34 to 1,024 of all NP genes were analyzed. The trees were generated by the method described in the legend to Fig. 1. Abbreviations for the PB2 tree: SWIA30, A/Swine/Iowa/15/30 (H1N1); SW31, A/Swine/1976/31 (H1N1); SWTN77, A/Swine/Tennessee/24/77 (H1N1); SWGER81, A/Swine/Germany/2/81 (H1N1); WSN33, A/WSN/33 (H1N1); PR8-34, A/Puerto Rico/8/34 (H1N1); FM47, A/Fort Monmouth/1/47 (H1N1); LEN57, A/Leningrad/134/17/57 (H2N2); SING57, A/Singapore/1/57 (H2N2); ANN60, A/Ann Arbor/6/60 (H2N2); KOREA68, A/Korea/426/68 (H2N2); NT68, A/NT/60/68 (H3N2); KIEV79, A/Kiev/59/79 (H1N1); CHILE83, A/Chile/1/83 (H1N1); MEM88, A/Memphis/8/88 (H3N2); SHIG97, A/Shiga/25/97 (H3N2); FPV34, A/Chicken/FPV/Rostock/34 (H7N1); FPVWEY, A/Chicken/FPV/Weybridge/34 (H7N7); CHK258-97, A/Chicken/Hong Kong/258/97 (H5N1); HK156-97, A/Hong Kong/156/97 (H5N1); BUDHOK77, A/Budgerigar/Hokkaido/1/77 (H4N6); GULMD77, A/Gull/Maryland/704/77 (H13N6); MALNY78, A/Mallard/New York/6750/78 (H2N2); RTNJ85, A/Ruddy Turnstone/New Jersey/47/85 (H4N6); TYMN80, A/Turkey/Minnesota/833/80 (H4N2); SEAMA82, A/Seal/Massachusetts/133/82 (H4N5); GULAST84, A/Gull/Astrakhan/227/84 (H13N6); ELON73, A/Equine/London/1416/73 (H7N7); EKY86, A/Equine/Kentucky/2/86 (H3N8). Abbreviations for the NP tree; SWIA30, A/Swine/Iowa/15/30 (H1N1); SWMAY54, A/Swine/May/54 (H1N1); SWWI57, A/Swine/Wisconsin/1/57 (H1N1); SWTN77, A/Swine/Tennessee/24/77 (H1N1); SWONT81, A/Swine/Ontario/2/81 (H1N1); SWIA88, A/Swine/Iowa/17672/88 (H1N1); SWNEB92, A/Swine/Nebraska/1/92 (H1N1); MD91, A/Maryland/12/91 (H1N1); WS33, A/Wilson-Smith/33 (H1N1); USSR77, A/USSR/90/77 (H1N1); ENG55, A/England/19/55 (H1N1); NT68, A/NT/60/68 (H3N2); SWDAN83, A/Swine/Dandong/9/83 (H3N2); MEM88, A/Memphis/2/88 (H3N2); SHIG97, A/Shiga/25/97 (H3N2); TYMN81, A/Turkey/Minnesota/1661/81 (H1N1); FPV34, A/Chicken/FPV/Rostock/34 (H7N1); BUDHOK77, A/Budgerigar/Hokkaido/1/77 (H4N6); OYSGER87, A/Oystercatcher/Germany/87 (H1N1); DKAUS80, A/Duck/Australia/749/80 (H1N1); ANASPRI76, A/Anas Acuta/Primorje/695/76 (H2N3); SWHK93, A/Swine/Hong Kong/168/93 (H1N1); SWGER81, A/Swine/Germany/2/81 (H1N1); SWNET85, A/Swine/Netherlands/12/85 (H1N1); SWENG92, A/Swine/England/195852/92 (H1N1); SWGER91, A/Swine/Germany/8533/91 (H1N1); SWSCH93, A/Swine/Schleswig-Holstein/1/93 (H1N1).

FIG. 3

Alignment of HA1 amino acid sequences of SW98 viruses with that of A/Finland/339/95 (H3N2). The residues in open boxes are potential glycosylation sites; shaded residues denote the receptor-binding site; residues in reverse type represent amino acid changes that may have been derived from a human virus precursor (see text); underlined residues are antigenic sites (lowercase letters indicate discrete antigenic sites).