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Biomedical subjects

R L Heberling

Publications and source records attributed to R L Heberling.

At least 19 recordsLinked to original sources

The chemotactic, phagocytic, and microbial killing abilities of primate polymorphonuclear leukocytes (PML).

Functions of polymorphonuclear leukocytes including chemotaxis, phagocytosis, and microbial killing were investigated in baboons (Papio cynocephalus), cebus monkeys (Cebus apella), and marmosets (Saguinus oedipus). Cells from a group of normal adult human volunteers were also studied for comparison. Polymorphonuclear leukocytes from the three nonhuman primate species were comparable to each other and to humans in chemotactic activity using endotoxin activated serum. In addition, the ability of blood leukocytes to ingest and kill microorganisms was investigated using a new fluorochrome microassay. Leukocytes of all non-human primates were competent in phagocytosing bacteria, but leukocytes from cebus monkeys and marmosets ingested candida organisms poorly. Compared to humans, all nonhuman primates exhibited poor killing of the microbes.

Animals

Fetal infection of the baboon (Papio cynocephalus) with lymphocytic choriomeningitis virus.

Recent observations of LCM-induced fetal damage in humans suggested attempts to develop an animal model for studies on viral congenital malformations. We report herein viral studies on three pregnant baboons (Papio cynocephalus) inoculated subcutaneously with LCM virus strain WE3. The first animal, inoculated in the 9th week of pregnancy, aborted 9 days after a high virus dose. Inoculation of the second baboon during a later stage (23rd week) of pregnancy with a moderate virus dose, resulted in the demonstration of virus in the placenta, amniotic fluid, and cord blood. The infant showed only a slight pleocytosis of the spinal fluid, but no virus shedding and no late sequelae. The third baboon inoculated with a high virus dose during the 21st week of pregnancy delivered an underweight, icteric infant that succumbed on the 6th day. All organs of this animal that were tested contained virus. Microscopic examination of these tissues revealed multifocal necrosis, cerebral glial nodules, meningitis, and bilateral choriovasculitis. These results illustrate that fetal damage observed in the LCM-inoculate baboon resembles that seen in humans following infection with LCM virus.

Animals

Expression of baboon endogenous virus in exogenously infected baboon cells.

Strains of low-passage, fetal diploid, baboon (Papio cynocephalus) fibroblasts were susceptible to exogenous infection with three independent isolates of baboon endogenous virus, as measured by an immunofluorescence assay specific for viral p28. Infectivity of the M7 strain of baboon endogenous virus for baboon cells of fetal skin muscle origin was equivalent to that for human and dog cells in that similar, linear, single-hit titration patterns were obtained. The assay for supernatant RNA-dependent DNA polymerase, however, showed that baboon cells produced only low levels of virus after infection compared with the production by heterologous cells. The results showed that baboon endogenous virus was capable of penetrating baboon cells and that viral genes were expressed in infected cells. Replication of complete infectious virus was restricted, however, indicating that in this primate system homologous cells differentially regulated the expression of viral genes.

Animals

Squirrel monkey retrovirus and Herpesvirus saimiri: observation in the same cell following isolation.

Electron microscopic examination of mink lung cells previously cultured with a squirrel monkey (Saimiri sciureus) throat swab suspension revealed the presence of squirrel monkey retrovirus (SMRV) and Herpesvirus saimiri (HVS) coexisting within the same cells in culture. HVS was identified by serum neutralization, and the retrovirus isolate was identified as SMRV by a morphologic examination, microimmunodiffusion analysis, and demonstration of an Mg2+ preference for the RNA-directed DNA polymerase.

Animals

Electron microscopic examination of primate feces for rotaviruses.

Using electron microscopic procedures known to be capable of detecting rotaviruses, feces from both human and nonhuman primates were examined for the presence of these viruses. Fecal samples were taken from man and animals with and without diarrhea. Rotaviruses were not observed in these specimens.

Animals

Experimental smallpox in chimpanzees.

In an attempt to prepare highly specific antiserum to variola virus, a chimpanzee was inoculated with a virulent human strain of this virus. Three uninoculated chimpanzees were housed in the same room; two of these developed clinical disease with seroconversion, while the third developed no evidence of infection and no antibody. The three animals that became ill also developed antibody to vaccinia and monkeypox viruses. Human contacts during the study and following a break in containment showed no evidence of infection as determined by serological tests and lack of clinical disease.

Animals

Observation of togavirus-like particles in nonhuman primates.

Particles resembling togaviruses were observed by electron microscopy in the urinary bladder lamina propria of one capuchin monkey and in placental syncytiotrophoblasts of one baboon. Type C viruses were observed in the baboon placenta, but not in the tissues of the capuchin monkey.

Animals

Studies with the baboon endogenous virus and its pseudotype of murine sarcoma virus in marmosets.

Three marmoset species (Saguinus oedipus oedipus, S. fuscicollis, Callithrix jacchus) failed to show evidence of infection or disease following inoculation of baboon endogenous type-C virus (BaEV). Cells infected with a Kirsten murine sarcoma-BaEV pseudotype (MSV[BaEV]) produced a progressive fibrosarcoma in S. o. oedipus and tumors in S. fuscicollis and C. jacchus which regressed. Tumor formation is believed to be due to growth of inoculated, virus-infected cells and not transformation of marmoset cells. S. o. oedipus showed the best serum neutralizing antibody response to BaEV and MSV(BaEV), S. fuscicollis a moderate response and C. jacchus no response.

Animals

Transfer factor and its protective effect against herpesvirus infections of marmosets.

Using skin test response and lymphocyte blastogenesis as indicators of cell-mediated immunity, we have been able to demonstrate in vivo transfer of cell-mediated immunity to marmosets both with dialyzable transfer factor (TFd) prepared from a human donor and transfer factor (TF) from baboon whole cell lysates. We were able to protect marmosets with TFd from fatal Herpesvirus hominis type 1 (HVH-1) disease. When TFd was administered prior to challenge with HVH-1, 50% of the marmosets survived. Of the untreated control animals and those first treated on day 0 or postinfection, 100% succumbed to disseminated HVH-1 disease. In addition, when TF prepared from TFd-treated marmosets which had survived HVH-1 disease, was given to other marmosets, it conferred protection from subsequent HVH-1 challenge.

Animals

Serodiagnosis of herpesvirus infection in primates.

The presence of herpesviruses in various animal tissues used for vaccine production is of importance, inasmuch as these viruses may go unrecognized, residing in latent form. Of greatest concern is Herpesvirus simiae (B virus) present in the majority of macaca species, one of the more extensively used laboratory nonhuman primates. The close antigenic relationship of B virus to human herpes strains (H. hominis) and SA8 (a baboon herpesvirus) makes serologic differentiation extremely difficult, but necessary. Complicating the differential diagnosis is the frequent infection of simian species with human strains. The present study clearly shows that many animal sera negative to herpes simplex will be negative to B virus in the neutralization test. However, a sufficient number of sera will be negative to simplex, but positive to B virus, indicating that the assumed one-way cross is invalid. Also, if antibody to simplex is present, and this antibody is present in most adult macaques, then differentiation requires testing with B virus. At least 50% of these positive sera may appear to be negative for B virus if only tested with H. hominis. Approximately 25% of the remaining positive sera will have higher titers to B virus than to herpes simplex and 25% will have the same titers to both viruses. Further, complement is required by many of the test sera to detect the presence of antibodies to B virus.

Animals

Oncornavirus: isolation from a squirrel monkey (Saimiri sciureus) lung culture.

An oncornavirus isolated from a squirrel monkey (Saimiri sciureus) lung culture has a density of 1.16 to 1.17 grams per milliliter, contains 70S RNA, and has an RNA-directed DNA polymerase that prefers Mg2+ over Mn2+ in an assay in which polyribocytidylate - oligodeoxyguanylate (12-18) is used as a synthetic template. Morphologically, the virus resembles Mason-Pfizer monkey virus but is antigenically distinct from this virus. The virus grows in cells of human, chimpanzee, rhesus monkey, canine, and mink origin, but not cells of squirrel monkey origin. On the basis of its properties, the newly isolated virus can be classified as a retravirus.

Animals

Endogenous New World primate retrovirus: interspecies antigenic determinants shared with the major structural protein of type-D RNA viruses of Old World monkeys.

A reverse transcriptase-containing virus has recently been isolated from a squirrel monkey (Saimiri sciureus). Molecular hybridization studies demonstrate that the squirrel monkey retrovirus (SMRV) is endogenous to this New World primate, yet lacks detectable nucleotide sequence homology with cellular DNAs of representative Old World primates or with the genomes of previously isolated Old World primate retroviruses. The 35,000-dalton major structural protein (p35) of SMRV was purified and shown to possess antigenic determinants distinct from those of known retroviruses. While SMRV was found to lack antigenic determinants broadly shared among mammalian type-C viruses, immunologic crossreactivity was demonstrated between SMRV p35 and the major structural protein (p26) of Mason-Pfizer monkey virus, a prototype type-D retrovirus of Old World monkeys. These findings support the concept that SMRV and Mason-Pfizer monkey virus are evolutionarily related, and raise the possibility that a progenitor of type-D retroviruses became genetically associated with primates at a very early time in their evolution.

Animals

Oncornavirus-like particles in squirrel monkey (Saimiri sciureus) placenta and placenta culture.

Oncornavirus-like particles similar in morphology to type D particles were observed in 1 of 2 squirrel monkey (Saimiri sciureus) placentas. Intracytoplasmic type A particles, immature virus particles, and mature viruses with eccentric or occasionally centric nucleoids were associated with placental syncytiotrophoblasts. A spike layer typical of type B viruses was not detected in viral envelopes. Onvornaviruses, identical to those previously isolated from squirrel monkey tissues and similar to Mason-Pfizer monkey virus, were seen in cultures derived from the virus-positive squirrel monkey placenta cocultivated with a mink lung culture. The major morphologic difference between the in vivo and the in vitro squirrel monkey virus was in the nucleoid position of mature virus particles.

Animals