Remote regulation of type 2 immunity by intestinal parasites.

The intestinal tract is the target organ of most parasitic infections, including those by helminths and protozoa. These parasites elicit prototypical type 2 immune activation in the host's immune system with striking impact on the local tissue microenvironment. Despite local containment of these parasites within the intestinal tract, parasitic infections also mediate immune adaptation in peripheral organs. In this review, we summarize the current knowledge on how such gut-tissue axes influence important immune-mediated resistance and disease tolerance in the context of coinfections, and elaborate on the implications of parasite-regulated gut-lung and gut-brain axes on the development and severity of airway inflammation and central nervous system diseases.

Rapid detection of type A influenza viruses with monoclonal antibodies to the M protein (M1) by enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay.

Monoclonal antibodies (MAbs) to the M protein (M1) were used in the development of direct detection systems for type A influenza viruses in clinical specimens. Optimal detection by an enzyme-linked immunosorbent assay was achieved when MAbs were used as capture antibodies and rabbit polyclonal antibodies were used as sandwich antibodies. Detection by the enzyme-linked immunosorbent assay required amplification of the virus. direct detection in clinical specimens (nasopharyngeal aspirates) was accomplished when MAbs recognizing two distinct antigenic sites of M1 were used in a time-resolved fluoroimmunoassay. Type A influenza viruses could be detected equally well in specimens obtained during epidemics of both H3N2 and H1N1 influenza viruses.

Monoclonal antibody analysis of influenza virus matrix protein epitopes involved in transcription inhibition.

Influenza virus M1 protein has been shown to inhibit viral RNA transcription, and in this study the epitopes on M1 critical for this function were localized. When a battery of 15 monoclonal anti-M1 antibodies were reacted with chemically cleaved fragments of M1 on a western blot, five distinct banding patterns were observed. A representative antibody was selected from each banding group, and its ability to reverse M1-effected transcription inhibition was measured. From these data, the sites on M1 critical for transcription inhibition were deduced. It appears now that the regions on M1 in the vicinity of amino acid residues #70 and #140 are critical for inhibition. Furthermore, by taking into account the hydropathicity and secondary structure, it is hypothesized that amino acids #70 and #140 are physically close together in the final three-dimensional conformation of M1 protein and that the residues in between form a loop and are thus removed from the functional site.

M protein (M1) of influenza virus: antigenic analysis and intracellular localization with monoclonal antibodies.

A panel of 16 monoclonal antibodies recognizing M protein (M1) of influenza virus was generated. Competition analyses resulted in localization of 14 monoclonal antibodies to three antigenic sites. Three monoclonal antibodies localized to site 1B recognized a peptide synthesized to M1 (residues 220 to 236) with enzyme-linked immunosorbent assay titers equivalent to or greater than that seen with purified M1; therefore, site 1B is located near the C terminus of M1. Sites 2 and 3 localize to the N-terminal half of M1. Antigenic variation of M proteins was seen when the monoclonal antibodies were tested against 14 strains of type A influenza viruses. Several monoclonal antibodies showed specific recognition of A/PR/8/34 and A/USSR/90/77 M proteins and little or no reactivity for all other strains tested. Immunofluorescence analysis with the monoclonal antibodies showed migration of M protein to the nucleus during the replicative cycle and demonstrated association of M protein with actin filaments in the cytoplasm. Use of a vaccinia virus recombinant containing the M-protein gene demonstrated migration of M protein to the nucleus in the absence of synthesis of gene products from other influenza virus RNA segments.

Immunologic response to influenza virus neuraminidase is influenced by prior experience with the associated viral hemagglutinin. II. Sequential infection of mice simulates human experience.

In man, vaccination with neuraminidase (NA) in H7N2 virus hybrids elicits greater anti-NA response than does N2 NA in H3N2 conventional vaccine, presumably because humans are H3 hemagglutinin (HA) primed and anti-H3 anamnestic response depresses concomitant N2 responses by antigenic competition. In a laboratory model, BALB/c mice were primed by different schedules of infection with H3N1, H3N2, and H3N7 viruses and given H3N2 and H7N2 vaccines equivalent in NA immunogenicity. In schedules using sequential infections, but not after a single infection with any virus, anti-N2 booster response was fourfold greater with H7N2 vaccine and was reciprocal to the magnitude of anti-H3 response. Thus, HA-influenced suppression of immunologic response to viral NA requires adequate HA priming but is not unique to man and can be studied in the murine model. An incidental finding of this study was the sharing of cross-reactive determinants by N1, N2, and N7 NA.

Vaccinia virus DNA sequences in the nucleus of persistently infected Friend erythroleukemia cells.

FL vac cell lines are Friend erythroleukemia cells persistently infected with vaccinia virus. These cells produce attenuated leukemia virus, virulent poxvirus, resist superinfection with vaccinia, and show high levels of spontaneous erythrodifferentiation and decreased tumorigenicity in syngeneic hosts (Pogo, G.T. and Friend, C. (1982) Proc. Natl. Acad. Sci. USA 79, 4805-4809). To determine whether resistance to superinfection was associated with the presence of vaccinia DNA in the nucleus, DNA from cells at different passage levels was hybridized to a vaccinia DNA probe. Vaccinia DNA sequences were detected in the nucleus of cells of lines that were productively infected with vaccinia. No such sequences were detected in productively infected with vaccinia. No such sequences were detected in productively infected L cells nor in persistently infected cell lines that no longer produced infectious particles but were resistant to superinfection. Although no evidence of integration of vaccinia DNA was observed, differences in the restriction patterns were detected at some passage levels. The presence of vaccinia virus DNA sequences in the nucleus apparently did not affect the size of the provirus, the integration pattern or the expression of the leukemia virus.