Biomedical subjects

C Sweet

Publications and source records attributed to C Sweet.

At least 55 records · Page 3Linked to original sources

PubMed1989

Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins.

Neonatal ferrets are protected against infection with influenza virus by milk-derived anti-influenza virus IgG after suckling on an immune mother. Live vaccines protect better than killed vaccines despite their stimulation of lower maternal haemagglutination-inhibiting antibody levels. This suggests that antibody to virus proteins other than the haemagglutinin may also be involved. To investigate this, adult ferrets were immunized intradermally with live vaccinia-influenza virus recombinants each expressing one of the 10 influenza virus polypeptides. Adult ferrets immunized with a recombinant expressing the H3 haemagglutinin were completely protected, and also passively protected their offspring, against a live challenge with clone 7a of the reassortant influenza virus A/Puerto Rico/8/34-A/England/939/69 (H3N2), immunity being mediated by IgG antibody. However, ferrets immunized similarly with recombinants expressing the H1 haemagglutinin, neuraminidase (N1 or N2), polymerases (PB1, PB2 or PAC), matrix protein (M1 or M2), nucleoprotein (NP) or non-structural proteins (NS1 or NS2) were completely susceptible to the influenza virus.

Animals↗

PubMed1989

Isolation and preliminary characterization of temperature-sensitive mutants of mouse cytomegalovirus of differing virulence for 1-week-old mice.

To study the pathogenicity of murine cytomegalovirus (MCMV) and to identify virulence determinants, we have isolated and phenotypically characterized a set of temperature-sensitive mutants. One mutant, PP269/38, was avirulent for 1-week-old BALB/c mice and restricted in its plaque formation and replication at 39 degrees C. Mutants PP242/68 and PP268/38 were 100-fold less virulent than salivary gland-grown virus (SGV), even after two passages in the salivary glands of 1-week-old mice. The former mutant was unable to replicate or form plaques at 39 degrees C whereas the latter replicated poorly at 39 degrees C but not at all at 40 degrees C although it was able to form plaques at 40 degrees C with a reduced plaque size. PP31/15 exhibited a 40-fold reduction in virulence compared to SGV after two passages in vivo and was unable to form plaques or to replicate at 40 degrees C; at 39 degrees C it was able to, with reduced efficiency. The remaining two mutants, PP99/3 and PP392/31, were 10-fold less virulent than SGV and were restricted at 40 degrees C. The six mutants have been classified into at least four complementation groups. These mutants may be useful for studying various aspects of MCMV pathogenicity.

Animals↗

PubMed1988

Role of upper respiratory tract infection in the deaths occurring in neonatal ferrets infected with influenza virus.

Passive immunization of ferret neonates by colostrally-derived anti-influenza virus IgG did not entirely prevent infection when mothers were immunized with 1 or 2 doses of formalin inactivated vaccine with adjuvant (alhydrogel). Influenza virus replication was almost completely prevented in the lower respiratory tract but only slightly reduced in the upper respiratory tract leading to deaths in about 50% of the neonates. Such neonates showed at most only minor lesions in the lower respiratory tract but moderate to severe inflammatory changes in the upper respiratory tract of most animals. This supports previous results suggesting that deaths, reminiscent of the human sudden infant death syndrome (SIDS), may arise purely as a result of upper respiratory tract infection, possibly following obstruction of the airways.

Animals↗

PubMed1987

Differential production of endogenous pyrogen by human peripheral blood leucocytes following interaction with H3N2 or H1N1 influenza viruses of differing virulence.

Fever and other constitutional effects of influenza (headache, myalgia, listlessness, nausea, shivering, anorexia and depression) result from liberation of endogenous pyrogen (EP) from phagocytes. These effects are milder for recent H1N1 influenza virus isolates than for H3N2 strains. Interaction with human peripheral blood leucocytes in vitro showed that H1N1 strains, A/USSR/90/77 and A/Fiji/15899/83, elicited significantly less EP (as assessed by the rabbit pyrogen assay) than two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. Similar observations were made with UV-inactivated A/Fiji/15899/69 and clone 64c. These results are in accord with the differential severity of fever produced by these strains in ferrets when intranasally infected or intracardially inoculated with live and inactivated viruses. They show that influenza virus strains differ in capacity to induce EP from phagocytes. Furthermore, the observations with inactivated virus show that certain virion components are pyrogenic and differ in quantity or nature between strains. These results are important in relation to the differential severity of influenza epidemics and the reactogenicity of vaccine strains.

Animals↗

PubMed1987

Role of milk-derived IgG in passive maternal protection of neonatal ferrets against influenza.

Neonatal ferrets are protected against infection with influenza virus by colostral and milk-derived anti-influenza virus IgG after suckling on an immune mother. The levels of IgG elicited and then transmitted to neonates were similar when mothers were immunized by either live infection or killed vaccines. Maternal anti-influenza virus IgA and IgM appears not to cross the neonatal gut epithelium although both are present in maternal serum and milk.

Animals↗

PubMed1987

Production of passive immunity in neonatal ferrets following maternal vaccination with killed influenza A virus vaccines.

Neonatal ferrets may be passively immunized following maternal vaccination with formalin-inactivated influenza A virus vaccine, but the level of protection from partial to complete depends upon the number of doses used to vaccinate the mother, the presence or absence of aluminum hydroxide adjuvant, whether or not the mothers were 'primed' by prior infection with a serologically heterologous type A virus, and the age of the neonate at challenge. Neonates were completely protected up to 2 weeks of age, but susceptibility returned to nasal epithelium at 5 weeks and to lung at 7 weeks. Mothers immunized up to 9 months previously also partially or completely protected their offspring, this correlating with the maternal serum haemagglutination-inhibition (HI) antibody titre at the time of neonatal challenge, not the duration of immunity.

Adjuvants, Immunologic↗

PubMed1986

Molecular studies of the differential replication at pyrexial temperatures of two influenza viruses differing in virulence for ferrets.

Replication of a virulent clone (7a) of the reassortant influenza virus A/Puerto Rico/8/34-A/England/939/69 (H3N2) in ferret nasal turbinate tissue is less affected than that of an attenuated clone (64d) by temperatures which occur during pyrexia in ferrets. This is a factor which contributes to the difference in virulence of the two clones. The differential replication of the two clones at pyrexial temperatures has been reproduced in allantois-on-shell (egg-bit) cultures, and the synthesis of viral polypeptides and RNA species examined. This virus-host system was chosen because it was more convenient to use than organ cultures but, like the latter, might provide information relevant to the in vivo situation. With this system it was not possible to achieve single cycle replication: the observed effects are cumulative over several (2 to 3) cycles of replication (24 h) and therefore conclusions from them may not be as definitive as those from single cycle conditions. However, in cells infected with clone 64d both A(+) cRNA and polypeptide synthesis were little affected at 40 degrees C but levels were decreased by about 70-80% at 41 degrees C; A(+) cRNA and polypeptide levels were unaffected even at 41 degrees C with clone 7a. These reductions seem insufficient to account for the 10-fold reduction in infectious yields of clone 64d at 40 degrees C or the 100-fold and 10-fold reductions in yields of clones 64d and 7a respectively at 41 degrees C. There was no evidence of increased production of non-infectious virus at elevated temperatures by either clone. Levels of vRNA were considerably reduced at 40 and 41 degrees C for both clones, but the levels were considerably greater at all temperatures in clone 7a-infected cells than in those infected with clone 64d; vRNA levels were higher for clone 7a at 41 degrees C than for clone 64d at 37 degrees C. The different levels of vRNA do not reflect differences in the availability of template A(-) cRNAs since levels of these were similar for both clones at 37 and 40 degrees C and only reduced for clone 64d at 41 degrees C. Although the interpretation of these data is complicated by multiple cycles of replication it appears that limited availability of vRNA could be an important constraint on the ability of clone 64d to replicate at pyrexial temperatures.

Animals↗

PubMed1986

Severity of fever in influenza: differential pyrogenicity in ferrets exhibited by H1N1 and H3N2 strains of differing virulence.

Intracardial inoculation of large quantities (200 micrograms viral protein/kg body weight) of infectious or u.v.-inactivated purified influenza viruses into ferrets resulted in a rapid febrile response which was significantly lower for two recently isolated H1N1 viruses, A/USSR/90/77 and A/Fiji/15899/83, than for two virulent clones, 7a and 64c, of the A/Puerto Rico/8/34-A/England/939/69 (H3N2) reassortant virus system. These results, which are in accord with the severity of fever produced by these strains in intranasally infected ferrets, show that influenza virus strains can differ in their capacity to induce fever (probably reflecting a differential capacity to induce endogenous pyrogen from phagocytes) and indicate, since u.v.-inactivated strains are pyrogenic, that this may be due to differences between strains in the nature or amount of certain virion components.

Animals↗

PubMed1985

Recent H1N1 viruses (A/USSR/90/77, A/Fiji/15899/83, A/Firenze/13/83) replicate poorly in ferret bronchial epithelium. Brief report.

Three recent wild-type H1N1 influenza virus isolates (A/USSR/90/77, A/Fiji/15899/83 and A/Firenze/13/83) replicated poorly in organ cultures of ferret bronchial tissue compared with the replication of an H3N2 wild-type virus (A/England/939/69). All four viruses replicated well in nasal turbinate tissue. Examination of one H1N1 virus (A/USSR/90/77) in vivo showed heavy infection in the upper respiratory tract of ferrets but little in the lower respiratory tract. These results raise the possibility that the mildness of human influenza arising from the H1N1 strains may be due to lack of capacity to attack the lower respiratory tract as well as the presence of antibody in previously exposed persons.

Animals↗

PubMed1985

Severity of fever in influenza: studies on the relation between viral surface antigens, pyrexia, level of nasal virus and inflammatory response in the ferret.

Previous work has shown that fever in influenza of ferrets occurs following release of endogenous pyrogen from virus-phagocyte interaction in the upper respiratory tract (URT), and suggested that the poor inflammatory response and correspondingly low fever elicited by A/Puerto Rico/8/34 (H1N1), compared with H3N2 reassortant clones of A/Puerto Rico/8/34-A/England/939/69, were related to its H1 and N1 surface antigens. Nasal virus levels, inflammatory and pyrexial responses produced in ferrets by clones 31 (H3N1) and 64b (H1N2) of the same reassortant system suggested a connection between the H1 antigen and low inflammatory response, but results were not conclusive. Unlike A/Puerto Rico/8/34, two recent H1N1 isolates, A/USSR/90/77 and A/Fiji/15899/83, produced a high inflammatory response yet low fever despite large amounts of virus in the URT, suggesting that either no connection exists between the acquisition of the H1 antigen and production of a low inflammatory response, or the H1 antigen of recent isolates, whilst antigenically related to that of A/Puerto Rico/8/34, is biologically different.

Animals↗

PubMed1985

Further studies of the reasons for the lack of alveolar infection during influenza in ferrets.

Intratracheal inoculation of influenza virus in the ferret was followed by a more severe airway infection than that produced by nasal infection and was mainly bronchiolar rather than bronchial. Also, virus isolation from the alveolar zone of the lung together with immunofluorescence and immunoperoxidase techniques showed that some virus reached the alveoli. Nevertheless, there was no subsequent alveolitis suggesting the existence of a clearance phenomenon. Alveolar macrophages were shown to have phagocytosed virus in vivo and phagocytosis studies in vitro showed that two mechanisms could operate to eradicate the virus. First, a rapid destruction of virus and second an abortive cycle of replication which produced virus antigen but not infectious virus. Experiments with large doses of virus indicated that after intranasal inoculation little virus reached the alveoli so it would probably be quickly cleared by the macrophages.

Animals↗

PubMed1984

Differential replication of attenuated and virulent influenza viruses in organ cultures of ferret bronchial epithelium. Brief report.

In contrast to its abundant replication in ferret nasal epithelium in vivo and in vitro, comparable to that of the virulent strains, the attenuated influenza virus A/PR/8/34 produced much lower yields than the virulent strains in organ cultures of bronchial epithelium agreeing with its relative inability to infect the lower respiratory tract of ferrets. The replication of another attenuated strain showed different temperature characteristics in bronchial epithelium to that in nasal turbinate epithelium.

Animals↗

PubMed1984

The sensitization of mice with a wild-type and cold-adapted variant of influenza A virus. II. Secondary cytotoxic T cell responses.

Reductions in virus titres and the generation of enhanced cytotoxic T cell (Tc) activity in the lungs of mice primed either with a wild-type, parental (H2N2) influenza virus, A/AA/6/60, or a cold-adapted variant A/AA/6/60-ca and challenged 6 weeks later with a H1N1 A/WSN virus showed that both H2N2 viruses could sensitize the mice. A comparison of graded sensitizing doses of each virus showed that inocula of 10(6) tissue culture infective doses (TCID50) of the ca-variant or 10(3) TCID50 of the wild-type virus gave similar results. The spleens and lungs of normal mice were found to contain similar levels (circa 1/10(5) cells) of precursor Tc cells and the level in the lung did not increase 2 days after intranasal (i.n.) inoculation of A/WSN virus. Two and 6 weeks after priming mice with 10(5) TCID50 of either virus, the lungs contained about a 20-fold increase in the precursor Tc cell frequency. In contrast, sensitization with a sub-lethal dose of a mouse-adapted A/WSN virus caused a 100-fold or greater increase. Sensitization of mice with the parental but not the ca-variant virus caused an increase in frequency of precursor Tc cells in the spleens of the sensitized mice and this might reflect the very low level of replication of the ca-variant virus in the mouse lung.

Animals↗

PubMed1984

The role of cellular susceptibility in the declining severity of respiratory influenza of ferrets with age.

A comparison was made, both in vivo and in organ culture, between newborn (1-day-old) and suckling (15-day-old) ferrets of lower respiratory tract tissue infected with a virulent strain (clone 7a) of influenza virus. Newborn ferrets were killed by influenza virus following intranasal inoculation but suckling ferrets were almost as resistant as adult ferrets. In newborn ferrets there was a rapid, severe and progressive infection of lung tissue with infection of alveolar cells as well as those of bronchial and bronchiolar epithelium (assessed by monitoring virus infectivity and by fluorescent antibody staining). In suckling ferrets, as previously shown for adult animals, the lung infection was less severe, less persistent and confined to the epithelium of bronchi with only a small bronchiolar involvement and even less alveolar cell infection. These differences observed in vivo were repeated in organ cultures obtained from various areas of the lung. i.e. alveolar and airway epithelial cells of newborn ferrets exhibited a greater susceptibility than those of older ferrets. Thus, it appears that one factor determining the greater susceptibility of the lower respiratory tract of newborn ferrets is a greater inherent susceptibility of alveolar and airway epithelial cells to infection with influenza virus. Other factors may also be involved and have yet to be investigated.

Aging↗

PubMed1984

The role of lung development in the age-related susceptibility of ferrets to influenza virus.

Newborn (I-day-old) ferrets died following intranasal inoculation of influenza virus (clone 7a) but suckling (15-day-old) ferrets were almost as resistant as adult ferrets. Many of the deaths in newborn ferrets were consequent upon an increased lower respiratory tract infection. One reason for the latter was an increase in susceptibility of both ciliated epithelium and alveolar cells in newborn ferret lungs when compared with the corresponding cells in adult and suckling ferrets (Coates et al. 1984). Work reported here shows that the lungs of newborn ferrets possess a greater proportion of ciliated epithelium-lined airway in comparison with the lungs of suckling and adult ferrets. This situation might also contribute to the increased susceptibility of the lower respiratory tract although the difficulties of assessing this influence precisely are discussed. In addition, the occlusion of the narrower airways of the immature lung in the infected newborn ferret contributes to the increased respiratory complications.

Age Factors↗

PubMed1984

Role of maternal immunity in the protection of newborn ferrets against infection with a virulent influenza virus.

Intranasal infection of newborn ferrets with a virulent strain of influenza virus invariably resulted in their deaths following virus replication to high titre in both lung and nasal turbinates (Collie et al., 1980). However, a similar challenge of newborn ferrets born to mothers immunized by infection with virulent or attenuated viruses resulted in complete protection; no virus replicated in their lungs and little or no virus was isolated from their nasal turbinates. Protection appeared to be antibody-mediated since it was sub-type-specific and milk-derived since newborn ferrets born to non-immune mothers but fostered onto immune mothers exhibited a similar level of protection to neonates born to and suckled by immune mothers.

Animals↗

PubMed1983

The effects of maternal influenzal viraemia in late gestation on the conceptus of the pregnant ferret.

Pregnant ferrets were inoculated intra-cardially on day 30 of gestation with influenza virus. The animals were sacrificed on days 5 to 11 after inoculation and the products of conception including the uterus were examined virologically and histopathologically. The results indicate that the initial site of infection of the conceptus is the haemophagous organ and that spread occurs from this site to the endometrium, placental labyrinth and fetus. Lesions in the fetus are confined to the liver and respiratory tract. In the liver they may represent either a viral hepatitis or a secondary response to placental damage resulting in the stimulation of erythropoiesis. In the respiratory tract they first occur in the nasal sinuses and upper airways suggesting that infection is via the amniotic fluid rather than via the blood stream. The relevance of these findings to human pregnancy is discussed.

Amniotic Fluid↗

PubMed1983

Distribution of viral antigen with the lower respiratory tract of ferrets infected with a virulent influenza virus: production and release of virus from corresponding organ cultures.

Using fluorescent antibody techniques, a semi-quantitative survey has been made of the distribution of influenza virus antigen in the trachea, main bronchi, and three zones (hilar, intermediate and alveolar) of all four lung lobes of ferrets following intranasal inoculation of a virulent clone (7a) of the recombinant influenza virus A/PR/8/34-A/England/939/69 (H3N2). The results confirm the indications from our previous quantitative surveys of infectious virus and histological damage in these areas, namely that infection is confined largely to airway epithelium and is rare in the alveoli. Furthermore, in the lung zones, viral antigen resided mainly in the bronchial rather than bronchiolar epithelium. In attempts to identify the reasons for lack of alveolar involvement organ cultures of alveolar tissue, from which all major airways had been removed, produced levels of virus similar to cultures of bronchus and trachea and the hilar and intermediate lung zones which contain airway and alveolar tissue. Hence, the lack of alveolar infection in vivo must be due to factors which prevent virus attack of susceptible alveolar cells. However, these organ culture experiments showed that a contributing factor could be very poor release of virus from any alveolar cells that do become infected. In contrast, although cultures of bronchi produced less virus than those of nasal turbinates (the most susceptible tissue in vivo) they released a high proportion of their yield and this ease of release may contribute to spread of infection in vivo.

Animals↗