Biomedical subjects

M W McGregor

Publications and source records attributed to M W McGregor.

10 recordsLinked to original sources

PubMed1994

An influenza A (H1N1) virus, closely related to swine influenza virus, responsible for a fatal case of human influenza.

In July 1991, an influenza A virus, designated A/Maryland/12/91 (A/MD), was isolated from the bronchial secretions of a 27-year-old animal caretaker. He had been admitted to the hospital with bilateral pneumonia and died of acute respiratory distress syndrome 13 days later. Antigenic analyses with postinfection ferret antisera and monoclonal antibodies to recent H1 swine hemagglutinins indicated that the hemagglutinin of this virus was antigenically related to, but distinguishable from, those of other influenza A (H1N1) viruses currently circulating in swine. Oligonucleotide mapping of total viral RNAs revealed differences between A/MD and other contemporary swine viruses. However, partial sequencing of each RNA segment of A/MD demonstrated that all segments were related to those of currently circulating swine viruses. Sequence analysis of the entire hemagglutinin, nucleoprotein, and matrix genes of A/MD revealed a high level of identity with other contemporary swine viruses. Our studies on A/MD emphasize that H1N1 viruses in pigs obviously continue to cross species barriers and infect humans.

Acute Disease↗

PubMed1993

Antigenic and genetic analysis of a recently isolated H1N1 swine influenza virus.

Hemagglutinins (HA) of H1N1 swine influenza viruses isolated in the United States have remained antigenically and genetically conserved for many years. In contrast to such conservation, the HA of A/Swine/Nebraska/1/92 (Sw/Neb) could readily be distinguished from those of contemporary porcine viruses. Twenty-eight amino acid mutations differentiated the HA of Sw/Neb and A/Swine/Indiana/1726/88, the most recent H1N1 swine influenza virus for which HA sequence data were available. Among these differences were mutations at potential asparagine-linked glycosylation sites and charge changes at many residues. The Sw/Neb virus also could be differentiated from other swine influenza viruses in hemagglutination-inhibition assays with monoclonal antibodies to recent H1 swine HA. Nonetheless, overall sequence analysis of the HA and the nucleoprotein genes of Sw/Neb indicated that this virus was more closely related genetically to classic H1N1 swine influenza viruses than to H1N1 avian or human viruses. Infection of swine with Sw/Neb under experimental conditions induced clinical signs and lesions typical of swine influenza. However, affected swine in the field had high, persistent fevers, but relatively mild signs of respiratory tract disease. This study indicated that an antigenically and genetically novel variant of swine influenza virus was detected in the United States.

Amino Acid Sequence↗

PubMed1992

Hemagglutinin mutations related to antigenic variation in H1 swine influenza viruses.

The hemagglutinin (HA) of a recent swine influenza virus, A/Sw/IN/1726/88 (H1N1), was shown previously to have four antigenic sites, as determined from analysis of monoclonal antibody (MAb)-selected escape mutants. To define the HA mutations related to these antigenic sites, we cloned and sequenced the HA genes amplified by polymerase chain reaction of parent virus and MAb-selected escape mutants. The genetic data indicated the presence of four amino acid changes. After alignment with the three-dimensional structure of H3 HA, three changes were located on the distal tip of the HA, and the fourth was located within the loop on the HA. We then compared our antigenic sites, as defined by the changed amino acids, with the well-defined sites on the H1 HA of A/PR/8/34. The four amino acid residues corresponded with three antigenic sites on the HA of A/PR/8/34. This finding, in conjunction with our previous antigenic data, indicated that two of the four antigenic sites were overlapping. In addition, our previous studies indicated that one MAb-selected mutant and a recent, naturally occurring swine isolate reacted similarly with the MAb panel. However, their amino acid changes were different and also distant on the primary sequence but close topographically. This finding indicates that changes outside the antigenic site may also affect the site. A comparison of the HA amino acid sequences of early and recent swine isolates showed striking conservation of genetic sequences as well as of the antigenic sites. Thus, swine influenza viruses evolve more slowly than human viruses, possibly because they are not subjected to the same degree of immune selection.

Amino Acid Sequence↗

PubMed1973