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Biomedical subjects

P N Fultz

Publications and source records attributed to P N Fultz.

At least 91 records · Page 5Linked to original sources
PubMed1989

Cell-mediated immune proliferative responses to HIV-1 of chimpanzees vaccinated with different vaccinia recombinant viruses.

The only animal that can be reproducibly infected with HIV, and that thus provides an experimental system for testing the effectiveness of prototype vaccines, is the chimpanzee. We compared proliferative responses to HIV and to vaccinia virus (VV) antigens of lymphocytes taken at various times from chimpanzees vaccinated with recombinant VV expressing different HIV genes. Animals were immunized with the original VV strain, as control, or with constructs expressing gp160 (VV160) given exclusively or in combination with one or two other constructs producing p25 (VV25), F/3'-orf (VVF), or the human interleukin-2 (IL-2) gene, which was included in an attempt to amplify immune responses. Irrespective of the HIV gene utilized, lymphocyte proliferation to HIV was usually weak and rapidly decreased after each inoculation, contrasting with strong and sustained responses to VV. Lack of adequate recall reactivity after challenge with fixed autologous lymphocytes expressing VV-produced HIV antigens indicated that vaccination resulted only in low levels of HIV-specific memory cell priming. The use of IL-2-producing VV did not lead to increased responsiveness. Reactivity to soluble purified gp160, but not to p25, could be detected in PBL from animals that had received both VV160 and VV25, while immunization with VVF resulted in a significant response to this protein in one of two animals. The transient nature of T cell reactivity to HIV might explain why, in similar studies, chimpanzees were not protected from infection with live HIV.

Animals↗
PubMed1989

HIV infection of chimpanzees as a model for testing chemotherapeutics.

Following inoculation of chimpanzees, the human immunodeficiency virus (HIV) establishes a long-term persistent infection characterized by seroconversion and the presence in peripheral blood cells of recoverable virus which can be quantitated. Because most HIV-infected chimpanzees have developed no signs of clinical diseases or hematologic abnormalities, their virologic, serologic and other immune responses can be compared with those of asymptomatic HIV-infected persons. This analysis might lead to the identification of factors important in preventing the development of disease. There are now approximately 100 HIV-infected chimpanzees in the United States, and many of these animals could be made available for testing chemotherapeutic agents for the ability to alter virus load or to enhance immune responses.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Seroprevalence of HIV-1 and HIV-2 in Guinea Bissau in 1980.

To determine the past prevalence of HIV-1 and HIV-2 in West Africa, we tested 440 serum samples collected in 1980 from people living in rural areas of Guinea Bissau. The sera were screened for antibodies by enzyme immunoassay (EIA) using purified simian immunodeficiency virus (SIV) isolated from rhesus macaque monkeys (SIVmac) and then confirmed by immunoblot and immunofluorescence assays for antibodies to SIV, HIV-2, and HIV-1. Five of the serum samples were repeatedly reactive by all assays to both SIV and HIV-2. None were positive for antibodies to HIV-1 by immunofluorescence, immunoblot or radio-immunoprecipitation (RIP) assays, with the exception of one HIV-2-seropositive samples which reacted with HIV-1 glycoproteins by RIPA. Thus, in 1980, at least 1.4% (six out of 440) of a random sample of people in rural Guinea Bissau had been exposed to a virus highly related to HIV-2 and SIV. One of these subjects may have been dually infected with HIV-1 and HIV-2.

Animals↗
PubMed1987

Superinfection of a chimpanzee with a second strain of human immunodeficiency virus.

Two chimpanzees, one (C-499) infected with the acquired immunodeficiency syndrome-associated retrovirus type 2 (ARV-2) strain of human immunodeficiency virus (HIV) and one (C-560) infected with the lymphadenopathy-associated virus type 1 (LAV-1) strain of HIV, were inoculated with approximately 10(4) tissue culture infective doses of the reciprocal strain. At the time of the second inoculation, both chimpanzees had high titers of HIV-specific antibodies, including antibodies that neutralized both virus strains. After inoculation of the second strain of HIV, the antibody titers in both chimpanzees increased 4- to 10-fold, and in one chimpanzee (C-499), the numbers of infectious peripheral blood mononuclear cells (PBMC) increased 1,000-fold to levels that are comparable with those observed after primary HIV infections. By restriction enzyme analysis of virus recovered from PBMC, both ARV-2 and LAV-1 were identified in C-499, thus demonstrating that superinfection had occurred.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lack of transmission of human immunodeficiency virus from infected to uninfected chimpanzees.

Four uninfected chimpanzees were each housed in separate cages with an HIV-infected chimpanzee for six to twenty-nine months. Despite close daily contact, all uninoculated chimpanzees remained seronegative for HIV, and virus was never isolated from peripheral blood mononuclear cells of the uninfected chimpanzees. These data indicate that the probability of transmission from infected animals to humans is extremely low and also provide supportive evidence for lack of transmission of HIV by casual contact.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Isolation of a T-lymphotropic retrovirus from naturally infected sooty mangabey monkeys (Cercocebus atys).

Healthy mangabey monkeys in a colony at the Yerkes Regional Primate Research Center were found to be infected with a retrovirus related to human immunodeficiency virus (HIV). Virus was isolated from peripheral blood cells of 14 of 15 randomly selected mangabeys. All virus-positive animals had antibodies to the mangabey virus at the time of virus isolation and, in a retrospective study, 82% of mangabey serum samples obtained in 1981 had antibodies to the virus. The newly isolated retrovirus is (i) morphologically identical to HIV by electron microscopy; (ii) serologically related to the human virus by enzyme immunoassay, immunoblotting experiments, radioimmunoprecipitation, and neutralization; and (iii) cytopathic for human OKT4+ cells. The mangabey virus also shares these properties with the simian T-lymphotropic virus type III (STLV-III) recently isolated from diseased macaques and from healthy African green monkeys (STLV-IIIAGM). However, the mangabey virus, like STLV-IIIAGM, differs from both HIV and STLV-III in that it apparently does not cause clinical immunodeficiency or disease following natural infection of the host from which it was isolated. Comparison of the virus-host interactions of these isolates may be valuable in defining determinants of pathogenicity for cytopathic retroviruses.

Animals↗
PubMed1986

Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome.

The lymphadenopathy-associated virus (LAV) prototype strain of human T-lymphotropic virus type III/LAV was transmitted to juvenile chimpanzees with no prior immunostimulation by (i) intravenous injection of autologous cells infected in vitro, (ii) intravenous injection of cell-free virus, and (iii) transfusion from a previously infected chimpanzee. All five animals that received more than one 50% tissue culture infective dose were persistently infected with LAV or chimpanzee-passaged LAV for up to 18 months. During this time they developed no illnesses, but they exhibited various degrees of inguinal and axillary lymphadenopathy and significant reductions in rates of weight gain. Detailed blood chemistry and hematologic evaluations revealed no consistent abnormalities, with the exception of immunoglobulin G (IgG) hypergammaglobulinemia, which became apparent in one animal 6 months postinfection and continued at more than 1 year postinfection. Transient depressions followed by increases in the numbers of T4 cells to levels greater than normal were observed in all animals after virus inoculation. However, the number of LAV-infected peripheral blood cells decreased with time after infection. Results of enzyme immunoassays showed that all infected animals seroconverted to IgG anti-LAV within 1 month postinfection and that antibody titers remained high throughout the period of observation. In contrast, only three of the five LAV-infected chimpanzees had detectable IgM antibody responses, and these preceded IgG-specific serum antibodies by 1 to 2 weeks. Virus morphologically and serologically identical to LAV was isolated from peripheral blood mononuclear cells of all infected animals at all times tested and from bone marrow cells taken from one animal 8 months after infection. One chimpanzee that was exposed to LAV only by sharing a cage with an infected chimpanzee developed lymphadenopathy and an IgM response to LAV, both of which were transient; however, no persistent IgG antibody response to LAV developed, and no virus was recovered from peripheral blood cells during a year of follow-up. Thus, LAV readily infected chimpanzees following intravenous inoculation and persisted for extended periods despite the presence of high titers of antiviral antibodies. However, the virus was not easily transmitted from infected to uninfected chimpanzees during daily cage contact.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Differing responses of hamsters to infection by vesicular stomatitis virus Indiana and New Jersey serotypes.

Intraperitoneal injection of vesicular stomatitis virus, New Jersey serotype (VSV-NJ), into inbred LSH hamsters resulted in an inapparent infection and survival of the majority of the animals. Infectivity titrations of tissues from VSV-NJ-infected hamsters showed that little or no virus was present following infection. The few animals that died from VSV-NJ succumbed to neurological disease. This is in contrast to our previous work where we found that LSH hamsters are exquisitely sensitive to i.p. infection by VSV, Indiana serotype (VSV-IND), and that large amounts of VSV-IND could be detected in tissues. The 50% lethal doses of VSV-NJ and VSV-IND for LSH hamsters are approximately 10(7) pfu and 1 pfu, respectively. When peritoneal cells from LSH hamsters were infected in vitro with both VSV serotypes, the yields of VSV-NJ consistently were lower than yields of VSV-IND. The growth of the two serotypes in fibroblast and epithelial cell lines of hamster origin was similar. VSV-NJ was not more efficient than VSV-IND in inducing interferon in vitro or in vivo, and there appeared to be no difference in the sensitivities of the two serotypes to the antiviral activity of hamster interferon. Thus, i.p. infection with less than 10(7) pfu of VSV-NJ is avirulent for LSH hamsters and this avirulence may be due, in part, to partial intrinsic resistance of peritoneal macrophages to infection by VSV-NJ. When four LSH hamsters that had been immunized with VSV-NJ were challenged with 10(6) LD50 of VSV-IND, three of the four animals survived. Despite the fact that neutralizing antibodies to VSV-NJ did not cross-neutralize VSV-IND, five out of five LSH hamsters were protected by passive transfer of 1 ml of immune hamster anti-VSV-NJ antiserum prior to challenge with VSV-IND. This suggests an important role for non-neutralizing antibodies.

Animals↗
PubMed1985

The natural history of infection with the lymphadenopathy-associated virus/human T-lymphotropic virus type III.

Over half of the persons infected with the lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III), the retrovirus that causes the acquired immunodeficiency syndrome (AIDS), become persistently infected with the virus. These "carriers" serve as the major reservoir of infection for others. Virus from their vascular and lymphatic spaces infects others through direct blood or mucous membrane exposure. After months to years, a high proportion of those infected will develop clinical manifestations of infection. For infected homosexual men, approximately 25% have developed AIDS-related conditions, mainly lymphadenopathy, and approximately 10% have developed AIDS. Because of the large number of infected persons in the United States, increasing rates of disease can be expected.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Vesicular stomatitis virus can establish persistent infections in Syrian hamsters.

Persistent infections by vesicular stomatitis virus (VSV) of the Indiana serotype were readily established in adult Syrian hamsters following intraperitoneal injection of the virus. Plaque-forming virus, identified as VSV by serological and physical criteria, was isolated from brain homogenates of five hamsters that were tested 3 to 8 months after infection. Four of these animals had exhibited either transient or permanent paralysis, whereas the fifth appeared healthy, during the period of observation. At the time of sacrifice all hamsters had high titres of anti-VSV-neutralizing antibodies in their sera.

Animals↗
PubMed1982

Mediators of protection against lethal systemic vesicular stomatitis virus infection in hamsters: defective interfering particles, polyinosinate-polycytidylate, and interferon.

Homologous defective interfering (DI) particles protected adult Syrian hamsters against lethal systemic infection with vesicular stomatitis virus (VSV) serotype Indiana. The DI particles had to be biologically active, but did not have to be administered at the same inoculation site as the infectious virus. Serum and tissue levels of VSV postinoculation were significantly lower in DI-protected animals than in unprotected controls, suggesting that true autointerference was occurring. However, some aspects of protection also must be mediated through nonspecific mechanisms, since susceptible hamsters could be protected against VSV Indiana by coinjection with heterologous DI particles prepared from VSV serotype New Jersey or by simultaneous administration of polyinosinic acid-polycytidylic acid. By measuring serum levels of putative hamster interferon (type 1), we found that animals coinjected with VSV and DI particles or polyinosinic acid-polycytidylic acid produced significant levels of interferon. Since similarly high serum levels of interferon were measured in recipients of VSV alone (animals that eventually died from infection), there appeared to be no correlation between protection against lethal disease and induced levels of serum interferon. Instead, serum interferon levels correlated positively with amounts of VSV PFU found in serum and tissues of infected animals, the lowest levels being found in serum of animals protected with homologous DI particles. The data are consistent with the hypothesis that autointerference by DI particles as well as various host defense mechanisms (possibly including induction of interferon) participates in protecting hamsters against lethal VSV infection.

Animals↗
PubMed1981

Genetic analysis of resistance to lethal infections of vesicular stomatitis virus in Syrian hamsters.

Vesicular stomatitis virus (VSV), Indiana serotype, causes a lethal disease in adult Syrian hamsters. Susceptibility to low doses of VSV (10 to 100 plaque-forming units) was shown to be genetically determined by examining six inbred strains. Three strains, LSH, MHA, and CB, were found to be extremely susceptible, with more than 70% of the animals dying within 72 h after intraperitoneal injection. Two strains, MIT and UT2, were intermediately susceptible, with approximately 60% of VSV-infected animals surviving. One strain, UT1, was found to be highly resistant; however, resistance was not acquired until the 4th or 5th week of age, and 100% of VSV-infected neonatal hamsters died. Analyses of F1 hybrid and segregant backcross populations derived from the LSH and UT1 strains suggested that at least three independent genetic loci contribute to phenotypic resistance. One locus resides on the X chromosome; the others reside on autosomes. No obvious linkage to the hamster major histocompatibility complex was detected. F1 hybrids of two highly susceptible strains, CB and MHA, were more resistant than either parental strain, suggesting that alleles of unlinked genes in the susceptible strains interact to produce a partially resistant phenotype. These alleles probably are the cause of the resistance phenotype found in the random-bred LVG strain which shares a common heritage with the CB and MHA strains.

Animals↗
PubMed1981

Involvement of cells of hematopoietic origin in genetically determined resistance of Syrian hamsters to vesicular stomatitis virus.

Susceptibility of Syrian hamsters of the inbred LSH and MHA strains to injection of as few as 10 plaque-forming units of vesicular stomatitis virus (VSV) was shown to occur only after intraperitoneal and intrapleural injection and not after injection of VSV intravenously, intranasally, or in the footpads. Despite the fact that fewer LSH hamsters died when VSV was injected via the latter routes, the histopathology of the VSV-induced disease at early times after infection was identical irrespective of the route of virus administration. Histological examination of tissues at various times after administration of VSV by the various routes revealed that VSV exhibited tropism for lymphoreticular tissue, with the greatest amount of necrosis in the splenic periarteriolar lymphoid sheath. A similar pattern also was observed in VSV-infected tissues from genetically resistant UT1 hamsters. Infectivity titrations of various tissues at different times after intraperitoneal injection of VSV revealed that resistant UT1 hamsters began to clear virus from tissues between 40 and 48 h postinfection, whereas virus titers remained high in susceptible animals. Resistance of UT1 hamsters appeared to require an intact spleen since survival of splenectomized animals was less than that of sham-splenectomized UT1 controls. Sublethal whole-body irradiation was also able to reduce resistance of UT1 hamsters (survival was reduced from 100 to 50%). Bone marrow cells from resistant (UT1 X LSH) F1 females were transferred into lethally irradiated susceptible LSH hamsters, and hematopoietic chimeras were produced. After intraperitoneal injection of 100 plaque-forming units of VSV, all of the female chimeras survived, but only 33% of male chimeras survived. These data indicate that resistance to VSV in Syrian hamsters is mediated, at least partially, by cells of hematopoietic origin.

Animals↗
PubMed1981

Wild-type isopropylmalate isomerase in Salmonella typhimurium is composed of two different subunits.

The isopropylmalate isomerase in Salmonella typhimurium is the second enzyme specific for leucine biosynthesis. It is a complex enzyme composed of two subunits which are coded for by two genes of the leucine operon, leuC and leuD. The two polypeptides have been shown to copurify through successive ammonium sulfate fractionations and have been identified on sodium dodecyl sulfate-polyacrylamide gels as having molecular weights of 51,000 (leuC gene product) and 23,500 (leuD gene product). They have also been shown to be fairly stable, since in vitro complementation of cell-free extracts of leuC and leuD mutant strains was demonstrated, with only a 40% loss of activity 16 h after preparation of the extracts. The native isopropylmalate isomerase was shown to have a Km for its substrate alpha-isopropylmalate of 3 x 10(-4)M.

Genes, Bacterial↗