Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

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Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential

This review of the life cycle of the Epstein–Barr virus (EBV) explains how EBV establishes lifelong infection in a host with protective immunity against the virus. The authors also discuss the role of EBV in the development of post-transplantation lymphoma, Hodgkin's disease, and Burkitt's lymphoma.

Persistence of the Epstein–Barr Virus and the Origins of Associated Lymphomas

The influenza virus neuraminidase glycoprotein is a tetramer with a box-shaped head, 100 X 100 X 60 A, attached to a slender stalk. The three-dimensional structure of neuraminidase heads shows that each monomer is composed of six topologically identical beta-sheets arranged in a propeller formation. The tetrameric enzyme has circular 4-fold symmetry stabilized in part by metal ions bound on the symmetry axis. Sugar residues are attached to four of the five potential glycosylation sequences, and in one case contribute to the interaction between subunits in the tetramer.

Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution

The principal neutralizing determinant (PND) of human immunodeficiency virus HIV-1 is part of a disulfide bridged loop in the third variable region of the external envelope protein, gp120. Analysis of the amino acid sequences of this domain from 245 different HIV-1 isolates revealed that the PND is less variable than thought originally. Conservation to better than 80 percent of the amino acids in 9 out of 14 positions in the central portion of the PND and the occurrence of particular oligopeptide sequences in a majority of the isolates suggest that there are constraints on PND variability. One constraining influence may be the structural motif (beta strand--type II beta turn--beta strand--alpha helix) predicted for the consensus PND sequence by a neural network approach. Isolates with a PND similar to the commonly investigated human T cell lymphoma virus IIIB (HTLV-IIIB) and LAV-1 (BRU) strains were rare, and only 14 percent of sera from 86 randomly selected HIV-1 seropositive donors contained antibodies that recognized the PND of these virus isolates. In contrast, over 65 percent of these sera reacted with peptides containing more common PND sequences. These results suggest that HIV vaccine immunogens chosen because of their similarity to the consensus PND sequence and structure are likely to induce antibodies that neutralize a majority of HIV-1 isolates.

https://science.sciencemag.org/content/sci/249/4971/932.full.pdf

Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant.

In a living cell membrane-bound compartments are continuously either separated or united through fusion reactions, and literally thousands of such reactions take place every minute. The formation of membrane vesicles from pre-existing membranes, and their fusion with specific acceptor membranes, constitute a prerequisite for the transport of most impermeant molecules and macromolecules into the cell by endocytosis, out of the cell by exocytosis, and between the cellular organelles (Palade, 1975; Silverstein, 1978; Evered & Collins, 1982). Less frequent, but equally crucial, are fusion events in fertilization, cell division, polykaryon formation, enucleation, etc. (for reviews see Poste & Nicholson, 1978). Although a great deal is known about the properties and consequences of individual forms of membrane fusion in cellular systems, and about fusion in artificial lipid membranes, the molecular basis for the reactions remain largely unclear.

Membrane fusion proteins of enveloped animal viruses.

Influenza is unique among the viruses in its capacity to vary. Because of antigenic variation, it has proved impossible to control influenza by vaccination, and variation in virulence, host range and transmissibility influence the spread and severity of influenza epidemics. This variation is caused by sequence changes in the genes of the virus and this review summarizes recent information on the structure of the genes and their products, the way in which these vary and the effects of the changes on the biological activities of the virus.

Molecular mechanisms of variation in influenza viruses

The objective of this international collaborative study was to compare recent swine isolates of influenza viruses and determine whether significant antigenic differences among isolates from different areas of the world could be detected. H1N1 viruses isolated from pigs, birds and humans in 12 different countries were compared in haemagglutination-inhibition assays with post-infection ferret sera and monoclonal antibodies to H1N1 strains. Using A/NJ/8/76 as the reference strain, we found that recent swine isolates from Hong Kong, Italy, Japan, and the USA possess a haemagglutinin virtually indistinguishable from that of viruses typically associated with pigs, i.e., A/NJ/8/76. In contrast, recent swine isolates from several European countries (Belgium, Denmark, France, Federal Republic of Germany, and Spain) were distinguishable from A/NJ/8/76, as demonstrated by tests in the various laboratories. These studies suggest that the H1N1 viruses in pigs are antigenically heterogeneous and that the circulation of particular variants is associated with the geographical location of the animals. These results raise the question of whether these viruses originated from the same source, i.e., pigs, and have undergone antigenic drift or, alternatively, were introduced from other hosts, such as birds.

Antigenic comparisons of swine-influenza-like H1N1 isolates from pigs, birds and humans: an international collaborative study

Influenza A virus strains isolated in the United States of America from ring-billed and Franklin gulls (Larus delawarensis, L. pipixcan) were found to possess a haemagglutinin (HA) antigen distinct from those of the twelve previously designated haemagglutinin subtypes of influenza A virus. Serological assays with antisera to reference strains representing the HA subtypes 1-12 and to a gull isolate, A/gull/Maryland/704/77, showed that the haemagglutinin of the gull virus was not related antigenically to the previously designated subtypes. In addition, comparison of the nucleotide sequences, and deduced amino acid sequences, of the 3′ region of the RNA genes coding for haemagglutinin indicated that the gull viruses represent a genetically distinct group. We propose that this new HA antigen, which has so far been detected only in gulls, be designated H13 and that A/gull/Maryland/704/77 (H13N6) be designated the reference strain for this subtype.

G. C. Schild

Papers

Molecular mechanisms of variation in influenza viruses

Antigenic comparisons of swine-influenza-like H1N1 isolates from pigs, birds and humans: an international collaborative study

Characterization of a novel haemagglutinin subtype (H13) of influenza A viruses from gulls