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Frozen serial serum specimens obtained from past studies on the natural history and prevention of Type B hepatitis in children were retested by radioimmunoassay for the following markers of hepatitis B infection: hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), and antibody to hepatitis B core antigen (anti-HBc). The interval between exposure and evidence of viremia (HBsAg) was as short as six days. HBsAg and HBeAg persisted for two to five months and occasionally for more than one year after recovery. After the disappearance of their respective antigens, anti-HBc and anti-HBs persisted for more than seven years and anti-HBe for one to two years. Treatment with hepatitis B immune globulin after exposure induced complete or partial protection or prolongation of the incubation period. Administration of heat-inactivated hepatitis B virus, MS-2 strain, to 29 children induced an inapparent infection in three, characterized by a transient appearance of HBsAg and HBeAg, and the persistence of anti-HBc, anti-HBe and anti-HBs for more than two years.

Immune responses in vitro of some species of marmosets to herpesvirus-associated antigens expressed on virus-transformed lymphoblastoid cell lines (LCL) were studied by determining lymphocyte proliferation, interferon production, and the induction of cytotoxic effector cells in mixed lymphocyte-LCL cultures (MLLC). Autologous Epstein-Barr virus (EBV)-transformed B-cell lines induced neither lymphocyte proliferation nor interferon production in MLLC, while autologous Herpesvirus ateles (HVA)-transformed T-cell lines stimulated responder cell DNA synthesis and interferon production. Both EBV-LCL and HVA-LCL failed to induce cytotoxic effector cells in autologous MLLC responder cells. These findings differ markedly from the human immune response to autologous EBV-LCL in vitro and may have implications for the unusual susceptibility of marmosets to the induction of lymphoproliferative disease following inoculation with oncogenic herpesviruses.

One hundred sixty-three persons immunised against hepatitis B with a vaccine containing HBsAg either of adw or ayw subtype were examined for antibodies against the a, d, and y determinants of HBsAg. Sera were tested for antibodies against HBsAg adw and HBsAg ayw separately by a solid-phase radioimmunoassay using polystyrene beads coated with HBsAg of either adw or ayw subtype, and the relative amounts of antibodies against the single determinants were calculated. After the third immunisation, all vaccinees had antibodies against the common determinant a. A quantitative evaluation showed that on average about 50% of HBsAg-specific antibodies were directed against the a determinant, and about 50% against d or y, respectively. However, as only anti-a is protective against cross-infection with other HBsAg subtypes, the degree of immunity of a person vaccinated against hepatitis B should be evaluated by the determination of antibodies to a rather than antibodies against total HBsAg.

Hepatitis A virus (HAV), when inoculated into cultures of the PLC/PRF/5 cell line which produces the surface antigen of hepatitis B virus (HBsAg), showed growth characteristics different from those of other picornaviruses. Antigen of HAV (HAAg) is expressed only about 10 days after infection. No major impact on the overall macromolecular biosynthesis of the host cells is observed. The growth rate of HAV-infected and uninfected cells was comparable, although the plating efficiency of infected cells was lower. Different hormonal factors were tested for their ability to stimulate viral antigen expression. Dexamethasone or prostaglandin E1 added to the culture medium increased HAAg expression; insulin reduced expression. Persistent infection of hepatoma cells by HAV never led to a cytolytic infection. In temperature-shift experiments, an adverse effect on the expression of HAAg and HBsAg was observed. In all experiments, the amounts of HBsAg in HAV-infected cells were reduced. On the whole, no major influence on host-cell metabolism is observed in cells persistently infected with HAV. Cell-mediated immunological response as a mechanism of pathological changes in HAV-infected liver is, therefore, more likely than a cytopathological effect.

Feline leukemia virus (FeLV) and simian sarcoma virus (SSV-1/SSAV-1) each contain six proteins which were separated by gel filtration in 6 m guanidine hydrochloride. The major protein both of FeLV and of SSV-1/SSAV-1 has species and interspecies antigenic determinants, and both viruses contain additional viral proteins with distinct species-specific antigenic determinant. The interspecies antigens of two primate C-type viruses (SSV-1/SSAV-1 and gibbon ape lymphoma virus) appear to be nearly identical and react only weakly with the corresponding antigens of lower animals.

Different population groups from the Shanghai area were surveyed by radioimmunoassay for serologic markers of previous infections with hepatitis A virus and hepatitis B virus. There were no significant differences in the prevalence of antibodies to hepatitis A virus (anti-HAV) in males and females, or in persons living in rural or urban areas. The prevalence of anti-HAV showed a biphasic increase with age, approaching 100% above age 50 years whereas the geometric mean titers declined. The rate of infection (attack rate) with hepatitis A among susceptibles in Shanghai declined appreciably between 1950 and 1960. The prevalence of hepatitis B markers also did not differ in the sexes, or in rural and urban populations. The patterns of prevalence of hepatitis B markers at different ages were compared to various theoretical mathematical models, and the data fitted best a model constructed from the assumption that two subpopulations of approximately equal size, one at low and the other at high risk, existed in the population groups studied. It was estimated that in Shanghai up to 12% of all individuals infected with hepatitis B became chronic hepatitis B surface antigen (HBsAg) carriers, although the overall prevalence of HBsAg carriers was only 6.9%. All HBsAg-positive individuals subtyped had been infected with hepatitis B virus of the subtype ad; 41.7% of HBsAg carriers also had hepatitis B e antigen (HBeAg), whereas in 32% of HBsAg carriers antibodies to HBe were present. Antibodies to HBsAg appeared to be lower in titer than in Western populations and to decline with age, and age-specific prevalence data indicated a relatively longer persistence of antibodies to hepatitis B core antigen.

Three lymphoblastoid cell lines were established from splenic lymphocytes of a lymphomatous baboon (Papio hamadryas) by co-cultivation of the lymphocytes with X-irradiated cells of marmoset or baboon lymphoblastoid cell cultures; the baboon splenic lymphocytes failed to grow when cultured alone. A herpesvirus, associated with each cell line, was identified by immunofluorescence, molecular hybridization and electron microscopy. Antigenic comparison with Epstein-Barr virus (EBV) showed that the baboon herpesvirus and EBV shared cross-reacting viral capsid antigens (VCA): 20 of 20 (100%) anti-VCA(EBV)-positive human sera and 55 of 62 (89%) baboon sera reacted with the baboon lymphoblastoid cells and baboon sera stained EBV VCA in P3HR-1 and EB-3 cells. No nuclear antigen, as assayed by anti-complement immunofluorescence tests, was detected in baboon lymphoblastoid cells when human or baboon anti-VCA positive sera were used. Baboon anti-VCA-positive sera also failed to stain EBV nuclear antigens (EBNA) in Raji or P3HR-1 cells. Preliminary molecular hybridization studies showed only approximately 40% homology between viral DNA of baboon cell lines and DNA of EBV derived from P3HR-1 cells. Proprietes D'Un Virus Herpetique Lymphotrope De Babouin Lie Au Virus D'Epstein-Barr Trois lignees cellulaires lymphoblastoides ont ete etablies a partir de lymphocytes spleniques d'un babouin (Papio hamadryas) lymphomateux, par coculture des lymphocytes avec des cellules irradiees aux rayons × provenant de cultures de cellules lymphoblastoides de marmouset ou de babouin; les cultures ne contenant que des lymphocytes spleniques de babouin ne se sont pas developpees. Un virus de l'herpes, associe a chaque lignee cellulaire, a ete identifie par immunofluorescence, hybridation moleculaire et microscopie electronique. Une comparaison antigenique avec le virus d'Epstein-Barr (EBV) a montre que le virus herpetique du babouin et l'EBV ont des antigenes capsidiaux (VCA) communs, a reactions croisees: les 20 serums humains anti-VCA-(EBV)-positifs (100%) et 55 des 62 serums de babouin (89%) ont reagi avec les cellules lymphoblastoides de babouin et les serums de babouin ont colore le VCA de l'EBV dans les cellules P3HR-1 et EB-3. Les tests d'immunofluorescence anti-complement n'ont mis en evidence aucun antigene nucleaire dans les cellules lymphoblastoides de babouin lorsque l'on a utilise des serums humains ou de babouin anti-VCA-positifs. Les serums de babouin anti-VCA-positifs n'ont pas colore les antigenes nucleaires de l'EBV (EBNA) dans les cellules Raji ou P3HR-1. Les etudes preliminaires d'hybridation moleculaire n'ont revele qu'une homologie d'environ 40% entre l'ADN viral des lignees de cellules de babouin et l'ADN de l'EBV provenant de cellules P3HR-1.

Hepatitis A virus (HAV) was isolated directly from human feces and propagated serially in an HBsAg producing human hepatoma cell line. No cytopathic effect was observed in the tissue culture and no detectable amounts of HAV were present in the tissue culture supernatant fluid. However, increasing amounts of hepatitis A antigen (HAAg) were detected by radioimmunoassay in the cell extracts obtained by freezing and thawing of cells. Specificity of the HAAg determination was shown by neutralization with convalescent sera of marmosets experimentally infected with the MS-1 strain of hepatitis A and by the absence of this neutralization with preinoculation sera. HAAg was first detected after four weeks in the cell extract of infected cultures after inoculation of 10(2)--10(4) tissue culture infectious doses of HAV from second passage.

Hepatitis A virus was purified from fecal samples collected at various times in the incubation period of patients with naturally acquired hepatitis A. The proteins of particles banding at around 1.34 g/ml in CsCl and sedimenting at about 160S were radioiodinated in vitro and separated by electrophoresis on polyacrylamide gels in the presence of 0.1% sodium dodecyl sulfate and 8 M urea. Under these conditions, the capsid proteins resolved into four polypeptides with molecular weights of approximately 31,000, 24,500, 21,000, and 9,000, respectively. A fifth protein of about 40,000 daltons in size and assumed to be equivalent to the precursor polypeptide VP0 of the picornaviruses was present in particles sedimenting at only 150 to 155S and banding at around 1.33 g/ml in CsCl. The physicochemical characteristics of these particles are consistent with those of the provirion structures of picornaviruses. In several of the fecal samples, these particles represented a considerable fraction of all particles present. The significance of this finding with respect to the antigenicity of hepatitis A antigen extracted from stool specimens is discussed.

Recombinant hepatitis B vaccine prepared from antigen expressed in yeast was given to 30 healthy young volunteers. Seroconversion rates and anti-HBs levels were compared with those in a control group matched for age and sex who had received plasma-derived hepatitis B vaccine. 4 weeks after the third immunisation results were similar in the two groups. In the recombinant vaccine group the immune response developed more slowly during the early phase and seroconversion rates and mean anti-HBs levels were slightly lower in males; this probably reflects use of a lower dose of recombinant vaccine (10 micrograms compared with 20 micrograms of the plasma vaccine). Side-effects were slight and antibody titres against Candida albicans were not increased in recipients of the recombinant vaccine.

Eighty-eight dialysis patients were vaccinated with recombinant hepatitis B vaccine prepared in yeast. Fourty-nine patients were immunized 3 times (months 0, 1, 6) intragluteally with 40 micrograms hepatitis B surface antigen (HBsAg) per dose. Only 32 of them (65.3%) showed anti-HBs concentrations above 10 IU/l with a geometric mean titer (GMT) of 180.7 IU/l after 3 vaccinations, whereas all of the 16 healthy controls, vaccinated 3 times with a 10-micrograms dose of the same vaccine batch, had specific antibodies higher than 10 IU/l (GMT 897.4 IU/l). Responses of patients were slightly higher than those of dialysis patients vaccinated in an earlier study with plasma-derived vaccine according to the same schedule. Results in 20 patients immunized 6 times intragluteally with 40 micrograms HBsAg/dose in monthly intervals were not better (at month 7, 65% showed anti-HBs concentrations greater than 10 IU/l; GMT = 126.6 IU/l), and 19 patients receiving 6 times 20 micrograms HBsAg monthly showed significantly lower responses (anti-HBs greater than 10 IU/l in 42% of vaccinees, GMT = 89.5 IU/l). The vaccine was tolerated well; side-effects were slight, and no serious adverse reactions were observed. In conclusion, recombinant hepatitis B vaccine is comparable to plasma-derived vaccine also in the case of dialysis patients; a 6-dose schedule does not seem to have much advantage compared to the conventional 3-dose regimen.

The influence of donor age on the production of interferon (IFN) alpha and IFN gamma by human peripheral blood mononuclear cells in vitro has been studied. The results demonstrate an age-related decline of the capacity to synthesize and secrete antiviral activity. Yields of virus-induced IFN alpha and lectin-induced IFN gamma were significantly decreased in mononuclear cell cultures from older subjects (greater than 50 years) when compared to those of younger subjects (less than 50 years). The observed deficiency of IFN production may be involved in the increased susceptibility of aged humans to viral infections and malignant diseases.

A single multisite intradermal (ID) administration of the same dose used for regular intramuscular (IM) immunisation with vaccine against tick-borne encephalitis virus (TBEV) resulted in seroconversion of all vaccinees within three weeks: with the regular IM schedule, two vaccinations were necessary for all vaccinees to seroconvert. After the first ID vaccination, antibodies of the IgM class against TBEV (anti-TBEV-IgM) were observed in all vaccinees; after the first IM vaccination, only three out of nine vaccinees showed an IgM response. The geometric mean titer (GMT) of anti-TBEV-IgM in seropositives was 5–20-fold higher in the ID group and similar to that after natural infection. The GMT of antibodies of the IgG class against TBEV (anti-TBEV-IgG) was also higher in the ID group but with a less marked difference. Hemagglutination-inhibiting (HI) antibodies appeared earlier and persisted longer after one or two ID injections; after a third vaccination, HI antibody levels were similar in both groups. Side effects after ID vaccination were limited to local reactions. These results indicate that follow-up injections may be omitted or at least reduced after ID administration of the vaccine dose usually used for IM vaccination schedules. However, additional studies in larger groups of vaccinees are necessary before ID vaccination can be recommended for general use.

Simian sarcoma virus, type 1 (SSV-1)-transformed non-producer cell lines were established by infection of normal marmoset fibroblast cells (HF) with limiting dilutions of SSV-1. Four focus-derived cell lines were identified as non-producers by assay of culture fluids for focus-forming activity and by the mixed culture cytopathogenicity test with XC cells. Further studies failed to detect production of type-C virus by 3H-uridine labelling, reverse transcriptase assay or electron microscopy. The non-producer cell lines, designated HF/SSV-NPI, IV, V, and VI, appeared morphologically transformed and cloned in soft agar with the same efficiency as HF/SSV-1 virus-producing transformed cells. Expression of either cytoplasmic or cell surface virus-related antingens was not detected by immunofluorescence or serum cytotoxicity tests. The presence of sarcoma genome in the transformed non-producer cell lines was demonstrated by rescue of focus-forming activity following superinfection with non-transforming helper virus or by cocultivation with helper-virus-producing cell lines. The SSV-1-transformed non-producer primate cells provide a useful tool for future studies.

F(ab′)2 fragment prepared by pepsin digestion of human IgG was used to raise antibody in goats. Adsorption of this antibody with whole IgG bound to Sepharose® yielded an antibody preparation which reacted specifically with the pepsin site of F(ab′)2. The adsorbed antibody was employed in a radioimmunoassay which was highly specific for the pepsin site. In measurements conducted on sera, the radioimmunoassay did not distinguish between F(ab′)2-like protein and naturally occuring antibody to the pepsin site. Results of assays showed the presence of pepsin site activity in all sera examined. In order to determine whether antigen or antibody was present, some of the sera were adsorbed with F(ab′)2 bound to Sepharose® and assays conducted after this treatment showed that the pepsin site activity was descreased. Thus, antibody to the pepsin site was present in these sera. Essentially the same levels of pepsin site activity were found in sera from normal individuals and from patients with cancer. Aboit 5–7 per cent of the sera in both groups had activities notably higher than the average level. Pepsin site activities in sera from patients with rheumatoid arthritis and lupus erythematosus were lower than the average level found in normal sera. To determine if this difference is significant, assays must be conducted on sera from more patients with these disease.

Cells transformed by simian sarcoma virus (SSV) express a 115000-dalton protein ( p115 ) that is precipitated by a goat antiserum to disrupted SSV/SSAV-infected and transformed cells but not by antibodies directed against the viral gag protein, p30, or envelope proteins. The protein is detected in productively as well as in nonproductively infected, transformed cells. It is not present in untransformed cells infected with helper virus (SSAV). The protein can be phosphorylated in vivo and in vitro at the tyrosine residue and SSV-transformed cells contain elevated levels of phosphotyrosine.

Cyclosporin A (CsA) was assessed for its effect on the production of antiviral activity by human peripheral blood leukocytes (PBL). CsA markedly reduced the production of interferon-gamma (IFN-gamma) in response to stimulation with lectin mitogens, bacterial products, alloantigens, or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL). CsA-mediated suppression of IFN-gamma secretion was dose-dependent and did not result from a shift of kinetics of the production of antiviral activity. The production of IFN-alpha in response to stimulation with Corynebacterium parvum (CP), viruses, and synthetic polynucleotides was not affected by the addition of CsA. These findings confirm earlier observations that CsA predominantly acts on T lymphocyte function. CsA may prove a valuable agent to study the role of IFN-gamma in the pathogenesis of virus-associated malignant lymphoproliferative disease.

The susceptibility of white-lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28--100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG-BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1 : 3 dilution. A HAV-baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3 : 1 by centrifugation of the GBG-BM pool); one group was treated at 140 degrees F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heat-treated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish-associated hepatitis A and retain the palatability of the shellfish.

Two enzyme immunoassays for the detection in immunoglobulin M (IgM) antibodies against tick-borne encephalitis virus were compared, employing a solid phase coated either with antigen or with mu-chain-specific antiserum to human IgM. The latter IgM-capturing assay system proved to be more sensitive, and its superiority was especially prominent when high titers of tick-borne encephalitis virus-specific IgG antibodies in addition to specific IgM antibodies were present in the sample. The application of this test is a valuable extension of the diagnostic tools for the rapid diagnosis of tick-borne encephalitis by IgM detection. Since specific IgG does not interfere, diagnosis can be readily established when patients have already developed high titers of IgG antibodies relatively late after the onset of the disease.

Publisher Summary Nonhuman primates have played an important role in the recent major and rapid advances in hepatitis research. Most nonhuman primate associated hepatitis outbreaks in man are caused by human hepatitis A virus, or an antigenically very similar or identical nonhuman primate hepatitis virus. The possible role of human hepatitis C (HC) viruses in these outbreaks cannot be evaluated because the agents have not yet been defined. Efforts to infect a large number of animal species, including the common laboratory varieties, various nonhuman primates, and somewhat more exotic species such as canaries, oysters, and mini-pigs, all met with negative results except for some sporadic and inconsistent positive findings in nonhuman primates, chiefly in chimpanzees. It was observed that nonhuman primates and particularly chimpanzees could transmit hepatitis to man and that “spontaneous” biochemically and histologically typical viral hepatitis occurred in recently caught chimpanzees. A major advance in hepatitis A research was the discovery of virus-like particles that could be agglutinated specifically by human convalescent sera in the early acute phase stools of human cases of hepatitis A (HA). The next advancement came with the description of standard serological tests, complement fixation, and immune adherence for a hepatitis A associated antigen and its corresponding antibody.

Three methods were compared for determining anti-HAV of the IgM class. In the first method flat-bottomed microtiter plates coated consecutively with anti-HAV of the IgG class and HAAg were incubated with patient serum and, after washing, peroxidase conjugated anti-mu was added. After subsequent incubation with substrate the enzymatic reaction was stopped and the optical density was measured. In the second method the solid phase was coated first with antibodies to IgM and after incubation with patient serum and subsequent incubations with HAAg and 125I anti-HAV of the IgG class radioactivity was counted. These two methods were compared with reorienting sucrose gradient ultracentrifugation, an established method for demonstrating specific IgM antibodies. The persistence of IgM anti-HAV in 103 sera drawn at different times after onset of jaundice was evaluated. Sera drawn up to 30 days after onset of hepatitis A were IgM anti-HAV positive with both of the first two methods. Forty-one to 90 days after onset of illness IgM anti-HAV could be demonstrated with the first method in 47% of the patients, in 94% with the second method, and in 82% with gradient centrifugation. The second method was most sensitive and could be adjusted so that at a serum dilution of 1:10(4) anti-HAV IgM was detected only up to six months after infection. In contrast to the first method, nonspecific reactions caused by rheumatoid factor were not detected with the second method. During a one-year period about 15,000 sera of patients with clinical diagnoses of acute hepatitis were tested; the positive results correlated well with the clinical data, and there was no indication of nonspecific positive results.

Canine thymus cells infected with virus (HL-23V) produced by human acute myelogenous leukaemia cells in culture were shown in previous reports to produce transforming and non-transforming type C virus similar or identical to the simian sarcoma virus complex SSV(SSAV) and to induce tumours in marmoset monkeys (Bergholz et al. 1977a). In these earlier studies the appearance of breakthrough foci at low dilutions of antiserum in neutralization tests with high-titred anti-SSV(SSAV) serum suggested the presence of another virus, distinct from SSV-(SSAV). We now report the isolation of this component and, by comparative neutralization analysis, demonstrate that it is most closely related to gibbon ape leukaemia virus (GALV). It is distinguished from SSV(SSAV) by kinetics of neutralization and molecular hybridization experiments. This component was readily cloned both from virus produced by HL-23V chronically-infected canine thymus cells established by Teich et al. (1975) when HL-23V was first isolated and from virus produced by HL-23V-induced marmoset tumour cells in culture. The presence of this component in the original leukaemic cell cultures is discussed.

A lymphocyte population of common marmosets (Callithrix jacchus) was identified by rosette formation with African green monkey erythrocytes; the rosette-forming cells appeared to be T lymphocytes, as approximately 62% of circulating lymphocytes and 85% of thymus cells formed rosettes with African green monkey erythrocytes. In addition, common marmoset lymphoid cells carrying T-lymphotropic Herpesvirus saimiri or Herpesvirus ateles formed rosettes with African green monkey erythrocytes and treatment of common marmoset circulating lymphocytes with an anti-T cell serum and complement (C′) eliminated rosette-forming cells. Common marmoset T lymphocytes apparently carry a surface receptor for African green monkey erythrocytes, but unlike humans and other closely related nonhuman primates, T lymphocytes of common marmosets fail to form rosettes with sheep erythrocytes.

Two strains of feline fibrosarcoma virus (ST-FeSV and GA-FeSV) were found to induce tumors in cats and marmosets, and to transform feline and marmoset cells in vitro after primary inoculation. A third strain (SM-FeSV) failed to induce tumors or transform marmoset cells after primary inoculation; however, when SM-FeSV-infected marmoset cultures were passed 26 times in vitro, the cell cultures released infectious virus which transformed marmoset fibroblasts but still failed to induce tumors in marmosets. ST-FeSV induced mainly round-cell type transformation (r foci), GA-FeSV induced predominantly mixed round-fusiform cell type transformation (fr foci), and SM-FeSV induced r and fr type foci with a higher proportion of fusiform cells in the fr foci than seen with GA-FeSV. Transforming virus was obtained from r or mixed r/fr foci of ST-FeSV but not from fr foci; heat treatment changed the virus from producing almost exclusively r type foci to inducing an increased number of fr foci. Passage of FeSV in cat cells yielded viruses with a higher ratio of infectivity for feline vs marmoset cells, while passage of FeSV in marmoset cells yielded virus with a relatively higher infectivity ratio for marmoset cells; the three strains differed in the degree of change in the infectivity ratio. Despite the alteration of host range of SM-FeSV propagated in marmoset fibroblasts, the virus retained feline P-30 antigen by CF and FA assays. Neutralization tests did not indicate but also did not exclude an alteration of the surface antigens of ST-FeSV or SM-FeSV propagated in marmoset fibroblasts. The alteration of the relative infectivity of FeSV during passage in marmoset cells may be due to: (1) the selection of a variant present in the original heterogeneous uncloned population; (2) mutation; or (3) recombination with some marmoset genetic material, possibly an as yet unidentified endogenous marmoset virus.

The incidence of the acquired immune deficiency Syndrome (AIDS) in North America has increased steadily since 1979. This Syndrome has been recognized mainly in male homosexuals in the Western hemisphere, in intravenous drug users, and occasionally in hemophiliacs and inhabitants of some tropical areas (Caribbean, Central Africa).

No differences in eventual immune-response rates were found between 325 subjects immunized passively/actively against hepatitis B and a control group of 108 subjects vaccinated only actively. The geometric mean titers of antibodies to hepatitis B surface antigen were nearly identical in controls and in a group of 87 individuals immunized passively/actively with the same vaccine lot. Lower geometric mean titers of antibodies to hepatitis B surface antigen were seen in 238 individuals who were vaccinated passively/actively with a different vaccine lot, a difference that may be explained by a somewhat lower immunogenicity in this particular lot. The mean half-life of hepatitis B immunoglobulin was calculated as 24.8 days, and in approximately 90% of vaccines 300,000 mIU of hepatitis B immunoglobulin provided protection until an active immune response had developed.

Three hundred and fifty-six bone marrow tissues obtained from patients of a general hospital were tested for spontaneous production after cultivation in vitro of interferon-like substances (ILS). Seventeen percent of the tissues produced ILS that protected human, but not chick, embryo cell cultures against the cytopathic effects of challenge virus infection. The incidence of ILS did not correlate with leukemia or other neoplastic diseases, or with any non-neoplastic disease.

Feline fibrosarcoma virus (FeSV) was assayed by focus formation in feline and marmoset fibroblast cultures overlaid with agar and re-fed with fluid media. The FeSV titers were consistent from experiment to experiment and were about four times higher in feline fibroblasts than in marmoset fibroblasts in parallel assays. Clones of FeSV-infected cells grown in soft agar, and foci of transformed cells produced by FeSV in monolayer cell cultures were both of two morphological types: round cells (r) and a loose meshwork of fusiform and round cells (fr). Thermal stability experiments indicated that the morphological differences of the foci were virus-dependent. The titration pattern of FeSV grown in marmoset or feline cells indicated that these preparations were either competent or contained an excess of helper virus. Preliminary challenge experiments with Snyder-Theilen FeSV grown in marmoset cells indicated that a 10- to 100-fold excess of non-transforming, interfering virus (helper virus) was present in this FeSV preparation.

Spontaneous and continuous production of an interference-inducing substance has been demonstrated in cultures of a cell line derived from a human myeloblastic leukemia. This substance had most of the characteristics of interferon.

Two newborn marmosets, inoculated with a cell-free extract of feline fibrosarcomas, developed multiple sarcomas and died within 46 days of inoculation, whereas two of these animals inoculated with a crude homogenate developed no tumors. This susceptibility to a mammalian RNA sarcoma virus suggests that marmosets may be particularly suitable for attempts to isolate infectious agents from man.

Marmosets inoculated with plasma from three early acute hepatitis patients developed hepatitis 30 to 40 days later. Other groups of marmosets receiving preinfection plasmas from the same patients showed no evidence of hepatitis in this experiment. It is, therefore, most probable that hepatitis in marmosets represented transmission of human disease rather than activation of latent "marmoset hepatitis."

Summary A comparison was made of 12 tissue culture cell lines of human origin with respect to their susceptibilities to a limited number of viruses. On the basis of the viral spectra obtained the lines could be divided into 2 groups corresponding to those established in morphological grounds. The observed interactions of the various viruses with the different cells fell into 4 categories: (1) viral multiplication with development of cytopathogenic effects; (2) propagation of virus in the absence of cellular destruction; (3) cytopathogenicity without viral replication; and (4) no growth of virus nor cellular damage. The implications of some of these findings have been discussed. Only cells of one of the groups (I) were susceptible to poliomyelitis, Coxsackie B and adenoviruses. None within group I were more sensitive to poliomyelitis than HeLa cells. Inoculation of cells of both groups with specimens from cases of infectious or serum hepatitis failed to yield evidence of infection.

Cultures of peripheral lymphocytes obtained during the acute phase of infectious mononucleosis (IM) were established. Mitomycin C-inhibited cells of these cultures caused abnormally high transformation rates in mixed cultures (MLR) with allogeneic peripheral lymphocytes and to a lesser degree they also stimulated autochthonous peripheral lymphocytes obtained from the same persons 3 to 9 months after their acute disease. This stimulation seems not to be caused by Epstein-Barr virus (EBV), present in the IM-cultures, because concentrated EBV preparations did not stimulate the convalescent lymphocytes and allogeneic lymphocytes from infants with and without circulating EBV antibodies responded equally well in the MLR with cultured IM lymphocytes. Circulating antibodies against surface antigens of autochthonous acute phase IM lymphocytes, stored in liquid nitrogen or cultured, were demonstrated in convalescent IM sera by the indirect membrane fluorescence technique. Blastogenic activity for both allogeneic and autochthonous lymphocytes was found in the cell-free supernatants of these IM lymphocyte cultures and was probably associated with cell membrane fragments.

The respiration and glycolysis of nine human cell lines grown in continuous tissue culture have been examined; 5 derived from normal and 4 from malignant tissues. In addition, 2 sublines of one strain were studied which were persistently infected with mumps and Newcastle disease viruses. The general metabolic patterns of respiration, anaerobic glycolysis, and aerobic glycolysis were similar for all the uninfected cell lines. The observed metabolic values appear similar to those reported for slices of malignant tissues. It cannot be concluded on this basis whether all the cells studied are of a “malignant variety” or whether all cells established in continuous tissue culture develop a metabolic behavior similar to that of cancer tissue. Metabolic measurements on the persistently infected lines revealed no significant changes in respiration. However, the cultures carrying Newcastle disease virus exhibited a marked increase in aerobic glycolysis. Although the cell lines fall into two groups on the basis of their viral spectra and morphology, no outstanding differences were noted in the metabolic properties measured.

SummaryUpon inoculation of cultures of HeLa or monkey kidney epithelial cells with large amounts of several strains of mumps virus at various stages of chick embryo-adaptation lesions resembling “giant cells” were observed, which however were shown to be caused by a cytolytic property of the agents. This effect could not be maintained on serial passage when allantoically-adapted strains were employed. Cytolysis was specifically prevented by human mumps convalescent and post-vaccination sera but not, or to a lesser extent, by sera taken during the acute stage of the disease or prior to immunization. The cytolytic activity was found to be more resistant to ultraviolet light than the infectious property. The possible relation of the cytolytic effect to the hemolytic activity of the virus is discussed.