Biomedical subjects

J K Hilliard

Publications and source records attributed to J K Hilliard.

At least 19 recordsLinked to original sources

PubMed1992

Activation of B virus (Herpesvirus simiae) in chronically immunosuppressed cynomolgus monkeys.

Three of 14 cynomolgus monkeys given the highest dose of an immunosuppressive drug in a 6-month toxicology study developed B virus (Herpesvirus simiae) oral lesions after 3 months of dosing. This necessitated early removal of all high-dose monkeys from the study due to concerns related to B virus. The incidence and severity of parasitic (Oesphagostomum sp.) lesions of the large intestine were also increased in high-dose animals. Both B virus and Oesophagostomum are enzootic in macaques, and the lesions caused by them were considered secondary to chronic immunosuppression caused by the highest dose of the test compound. Evidence of immunosuppression included decreased lymphocyte counts (B-cells; CD2 and CD8 T-cells), histopathologic evidence of lymphoid suppression, and serum-induced inhibition of lymphocyte mitogen responses. Pathogenesis of the B virus was apparently associated with both activation of latent virus as well as transmission of active virus. Approaches for virologic monitoring of primates and for ensuring optimal safety for primate handlers are discussed.

Animals↗

PubMed1990

B virus (Herpesvirus simiae) infection in humans: epidemiologic investigation of a cluster.

A cluster of four cases of symptomatic B virus infection in humans occurred in Pensacola, Florida, in March 1987. Three cases occurred in persons who worked with monkeys at a research facility, and the fourth resulted from apparent autoinoculation through use of a nonprescription skin cream. Contact tracing identified 159 persons who may have been exposed to B virus (21 had been exposed to monkeys at the facility and 138 had been exposed to one or more of the case-patients), but no further cases were identified. Comparisons of restriction endonuclease patterns from B virus isolates linked two of the three cases in monkey handlers to one clinically ill monkey and the other to a second, healthy monkey. Three risk factors for human infection were identified: nonuse of mechanical or chemical restraints for monkeys before handling, nonuse of available protective gear, and direct viral inoculation through the application of a topical medication.

Acute Disease↗

PubMed1990

Ocular histopathologic findings in a case of human herpes B virus infection.

A 37-year-old male laboratory technician who sustained a cutaneous penetrating wound from a rhesus monkey developed a progressive ascending encephalomyelitis due to culture-proven herpes B virus (Herpesvirus simiae) infection. He died 6 weeks after his injury despite acyclovir and ganciclovir treatment that was initiated after central nervous system symptoms developed. Histopathological examination of the patient's left eye revealed a multifocal necrotizing retinitis associated with a vitritis, optic neuritis, and prominent panuveitis. Herpes-type virus was identified in the involved retina by electron microscopy. Postmortem vitreous cultures taken from both eyes and retinal cultures taken from the right eye were positive for herpes B virus. Herpes B virus produces infection and destruction of retinal tissues similar to other herpesviruses. To our knowledge, this case represents the first histopathologic demonstration of herpes B virus infection in a human eye.

Adult↗

PubMed1990

Nonhuman primate bites.

Nonhuman primate (monkey) bites to researchers and attending animal care staff may present problems in patient management. Such inoculations can transmit serious bacterial and viral infections to the human handlers. Significant local and systemic manifestations can subsequently develop following such an injury. Since Herpesvirus simiae (B virus) is enzootic in Asiatic monkeys of the genus Macaca, and since B virus infection in humans is usually fatal, additional prophylactic and therapeutic measures must be taken when persons are bitten by macaque monkeys. Primate bites require early aggressive intervention.

Acyclovir↗

PubMed1990

Seroprevalence of B virus (Herpesvirus simiae) antibodies in a naturally formed group of rhesus macaques.

Eighty-two percent of a group of rhesus monkeys removed from Cayo Santiago were seropositive for B virus (Herpesvirus simiae) antibodies. Similar results were obtained from the Cayo Santiago macaque population two decades ago and from feral Indian rhesus monkeys. Thus it is likely that B virus has been enzootic in the Cayo Santiago population since 1938, when the colony was established with stock imported from India.

Age Factors↗

PubMed1990

A cross sectional survey for B virus antibody in a colony of group housed rhesus macaques.

A systematic sampling technique was used in combination with a highly sensitive and specific ELISA to provide unbiased age-specific prevalence estimates of B virus antibody in rhesus monkeys housed in three different outdoor breeding corrals. Among 146 sampled monkeys, 97% of animals 2.5 years and older were seropositive, while only 22% of younger animals were seropositive. Neither gender nor social dominance ranking were predictive of B virus antibody status. The strong age association was not inconsistent with hypothesized venereal transmission of B virus. Improvements in the epidemiologic understanding of B virus are necessary to assist efforts to eradicate this agent from breeding colonies of rhesus monkeys.

Age Factors↗

PubMed1989

Simian alphaherpesviruses and their relation to the human herpes simplex viruses.

Biochemical and immunological properties of structural and non-structural polypeptides of the human simplex viruses (HSV1 and HSV2) and four related herpesviruses of non-human primates [Herpesvirus simiae (B virus), H. cercopithicus (SA8), H. saimiri 1 (HVS 1), and H. ateles 1 (HVA 1)] were compared. Using a radioimmunoassay (RIA), the presence of antigenic determinants shared among all six viruses was demonstrated. The relative degree of antigenic cross-reactivity among these viruses was further assessed by competition RIA. Antigenically, HSV 1 and HSV 2 were most closely related to each other although both SA 8 and B virus were also very closely related to HSV 1. Considerably less cross-reactivity existed between either HVS 1 or HVA 1 and the other four primate herpesviruses. Cross-hybridization between simian and human herpesvirus genomes demonstrated that extensive homology exists between each of the simian viruses and both HSV1 and HSV 2. Viral polypeptides bearing common antigenic determinants were identified by immune precipitation of infected cell polypeptides and by immunoblotting. Among the polypeptides of HSV which were recognized by antisera to simian viruses were the VP 5 and p40 proteins, both of which are structural components of the virion nucleocapsid. Using recombinant plasmids containing sequences of the HSV 1 VP5, p40, DNA polymerase, major DNA binding protein, and TK enzyme genes, homologous sequences were detected in all four simian viruses. Together, these results demonstrate that HSV 1, HSV 2, SA 8, and B virus form a closely related sub-group of the primate herpesviruses; HVS 1 and HVA 1 are also related to the other four primate herpesviruses, albeit more distantly.

Antigens, Viral↗

PubMed1989

Relatedness of glycoproteins expressed on the surface of simian herpes-virus virions and infected cells to specific HSV glycoproteins.

The antigenic relatedness of the surface glycoprotein antigens of six herpesviruses indigenous to human and nonhuman primates was examined. Binding of anti-viral sera to viral antigens expressed on the surface of infected cells demonstrated that the surface antigens of herpes simplex virus type 1 (HSV 1), HSV 2, simian agent 8 (SA8), and Herpesvirus simiae (B virus) exhibit extensive cross-reactivity. Surface antigens of two viruses isolated from South American primates, H. saimiri 1 (HVS 1) and H. ateles 1 (HVA 1), were comparatively more virus-specific in their antigenic reactivity. Endpoint neutralization tests performed in the presence and absence of complement confirmed these results. Immunoprecipitation of viral proteins was used to identify those representing cross-reactive surface antigens. A glycoprotein of approximately 110,000-125,000 Daltons (110-125 k) was immunoprecipitated from cells infected with each of the six primate herpesvirus by antisera to each of the viruses. Using monospecific antisera, these glycoproteins were shown to be antigenically related to the gB glycoproteins of HSV. Although these glycoproteins were antigenically conserved among all six viruses, antibodies to the gB glycoproteins did not cross-neutralize heterologous viruses. A glycoprotein of approximately 60-70 k was precipitated from HSV 1, HSV 2, SA8, and B virus infected cells by antisera to each of these four viruses. These SA8 and B virus glycoproteins were shown to be antigenically related to the gD glycoproteins of HSV 1 and HSV 2 and to be involved in cross-neutralization among these viruses. Antisera to HVS 1 and HVA 1 did not recognize these gD glycoproteins nor was a glycoprotein of similar molecular weight precipitable from HVS 1 or HVA 1 infected cells by antisera to the other four viruses. Southern blot hybridizations using probes for HSV glycoprotein genes confirmed the conservation of the gB glycoproteins among all the simian viruses and of the gD gene in SA8 and B virus. A glycoprotein of approximately 75-80 k was, however, precipitated from HVS 1 and HVA 1 infected cells by antisera to either of these two viruses. In addition, at least one glycoprotein which appeared to be predominantly virus-specific in its reactivity was identified for five of the viruses.

Animals↗

PubMed1989

Serological evidence for variation in the incidence of herpesvirus infections in different species of apes.

Sera from captive lowland gorillas, chimpanzees, orangutans, and gibbons were screened by enzyme-linked immunosorbent assay (ELISA) for antibody to herpesviruses serologically related to human herpes simplex virus types 1 and 2 (HSV-1, HSV-2), a baboon virus (SA8), and a macaque herpesvirus (B virus). The incidence of herpesvirus antibodies varied considerably among the different species, gorillas having the highest incidence of seropositivity (65.4%) and orangutans the lowest. The virus specificity of positive sera was further analyzed by examining the kinetics of virus neutralization, competition of reactivity in ELISAs, and immunoblotting against HSV-1, HSV-2, SA8, and B virus antigens. Using these assays, the majority of positive gorilla sera (49 of 53, 92%) were determined to react in a manner identical to human HSV-1 immune sera. The remaining four positive gorilla sera reacted as HSV-2-positive sera. In contrast, the majority of positive chimpanzee sera (5 of 7, 71%) reacted as HSV-2 immune rather than HSV-1 immune. All positive sera from gibbon apes reacted as HSV-1 positive. No orangutan sera were identified which gave positive reactions by ELISAs to any of the four primate herpesviruses tested. Although four orangutan sera gave equivocal results against HSV-1 antigen, further analysis by immunoblotting could not confirm any specific reactivity with any of the primate herpesvirus antigens. Varied reactivity among individual animals with both SA8 and B virus proteins was observed, but none of the seropositive primates detected appeared to be infected with either of these simian viruses. Three gorilla sera had antigen recognition patterns slightly different from those of HSV-2-positive human and chimpanzee sera and another HSV-2-positive gorilla serum, raising the possibility that these animals harbor an indigenous virus related to HSV-2.

Animals↗

PubMed1989

Serological survey for viral diseases in the Cayo Santiago rhesus macaque population.

The free-ranging population of rhesus monkeys (Macaca mulatta) on Cayo Santiago was sero-surveyed for human measles, simian virus 40, B virus (Herpes simiae), rhesus cytomegalovirus, human and simian retroviruses and encephalomyocarditis virus to determine the prevalence of these viruses in the colony. The results of this study indicate that the colony is free of SV40, HTLVIII (HIV-1), STLVIII (SIV) and SRV1; has a low prevalence of measles and EMCV; and high prevalence rates for B virus, CMV and HTLVI.

Academies and Institutes↗

PubMed1988

A naturally occurring epizootic of simian agent 8 in the baboon.

An epizootic of genital lesions was observed on baboons (four Papio sub-species) housed in two different outdoor breeding corrals. Serological analysis revealed strong prevalence of antibodies to Simian Agent 8 (SA8). This herpesvirus was subsequently recovered from skin lesions and identified by restriction endonuclease digestion of infected cell DNA. Observations of lesion type, frequency and location were suggestive of venereal transmission. The remarkable similarity between infection resulting from SA8 in baboons and herpes simplex virus in man suggests that the baboon is an excellent model in which to study genital herpes virus transmission and infection.

Age Factors↗

PubMed1987

Herpesvirus simiae (B virus): replication of the virus and identification of viral polypeptides in infected cells.

The events and products of replication of Herpesvirus simiae (B virus) in Vero cells were studied. The time course of the synthetic events of DNA replication and protein synthesis were found to be similar to the processes of the herpes simplex viruses and SA 8. Infectious progeny virus were detected by 4 hours post infection and were first found extracellularly between 6 and 8 hours post infection (PI). As in the case of SA 8, all cell lines tested were permissive for lytic infection by B virus. Analyses of B virus-infected cells by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) revealed approximately 50 infected cell polypeptides (ICP) ranging in molecular weight from about 26,000 to 239,000 daltons. The kinetics of synthesis of the ICPs were also identified. At least nine glucosamine-containing glycopeptides were noted ranging from 133,000 to 29,000 daltons.

Animals↗

PubMed1987

Human milk-derived lactoferrin inhibits mitogen and alloantigen induced human lymphocyte proliferation.

Purified lactoferrin (LF), isolated from human milk, was tested for its effect on human T-lymphocyte proliferative responses to phytohemagglutinin (PHA) and to alloantigens in mixed lymphocyte culture. LF inhibited proliferation in both assays in a dose-dependent manner. The suppressive effect was not due to LF mediated cytotoxicity since washing cells that had been pre-incubated with LF restored their proliferative activity. LF was most effective in suppressing the PHA response when added within 24 h of culture initiation. Iron saturated LF failed to inhibit PHA-induced proliferation, suggesting that the mechanisms of suppression involve the chelating property of LF. The suppressive effect of LF on T-lymphocyte proliferative response in vitro supports the notion that LF has significant immunoregulatory potential in vivo.

Female↗

PubMed1986

Comparison of the primate alphaherpesviruses. I. Characterization of two herpesviruses from spider monkeys and squirrel monkeys and viral polypeptides synthesized in infected cells.

Biological and biochemical properties of two neurotropic herpesviruses of New World monkeys--Herpesvirus saimiri type 1 (HVS-1) and Herpesvirus ateles type 1 (HVA-1)--were examined and compared. HVS-1 and HVA-1 both exhibited a time course of replication similar to another primate herpesvirus, SA 8. Both viruses grew rapidly and high titers of infectious virus were readily produced. HVS-1 and HVA-1 were also able to replicate efficiently in cell lines derived from a number of primate and non-primate species. Analysis of proteins synthesized in infected cells revealed the presence of over 30 virus-specific proteins ranging from less than 30,000 to over 200,000 daltons apparent molecular weight. Both viruses specified synthesis of a major capsid polypeptide of 148,000 daltons. Pulse labeling of cells during infection demonstrated temporal differences in the kinetics of synthesis of individual viral proteins and post-translational modification of a number of viral polypeptides. Glycosylated polypeptides synthesized in HVS-1 and HVA-1 infected cells were identified which ranged from approximately 49,000 to 120,000 daltons. Structural polypeptides of HVA-1 and HVS-1 virions were identified by SDS-PAGE analysis of purified virions. Taken together with clinical data on the diseases caused by these viruses, these studies indicate that HVS-1 and HVA-1 appear similar in many respects to both the human herpes simplex viruses and alphaherpesviruses of other primates.

Animals↗

PubMed1986

ELISA for detection of IgG and IgM antibodies to HSV-1 and HSV-2 in human sera.

A rapid, enzyme-linked immunoassay (ELISA) was applied to identify and measure specific IgG and IgM antibodies to herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2). Detergent solubilized infected cells and mock-infected cells were used as antigens in the assay. Identification of type-specific antibodies was achieved by a competition assay in which clinical sera mixed with HSV-1 or HSV-2 antigens were assayed for reactivity to identical antigens coating wells of polystyrene microtiter plates. Reactivity and the specificity of the reactive immunoglobulin class was quantitated using biotinylated goat anti-IgG and biotinylated goat anti-IgM. Five paired sera from patients with diagnosed herpes simplex genital infections and one human anti-HSV-1 reference serum were tested with this assay and results were compared to results previously obtained using a complement fixation test and micro-SPRIA. The results indicate that the ELISA is a specific, sensitive and simple test which confirms the herpes simplex virus infection history of patients.

Animals↗

PubMed1986

ELISA for detection of group-common and virus-specific antibodies in human and simian sera induced by herpes simplex and related simian viruses.

A rapid (3.5 h) enzyme-linked immunosorbent assay (ELISA) was developed for the detection of serum antibodies to herpes simplex virus type 1 (HSV-1) and to two antigenically related monkey viruses, simian agent 8 (SA8) and Herpesvirus simiae (B virus). Crude preparations of detergent solubilized infected cells and similarly treated control mock-infected cells served as antigens for coating wells in microplates. Biotinylated protein A and avidin-conjugated alkaline phosphatase were used to detect antibodies in sera from different species (humans, monkeys and rabbits). Three prototype assays are described with three degrees of specificity. Common or specific determinants on the viral antigens could be assayed in simple competition tests using similar antigen preparations to those coating the wells. The specific assays permitted rapid differential serodiagnosis of antibodies to human and simian herpesviruses.

Animals↗

PubMed1986

Rapid identification of herpesvirus simiae (B virus) DNA from clinical isolates in nonhuman primate colonies.

A rapid, simple technique, based on restriction endonuclease analysis of radioactively labeled infected cell DNA, is described for identification of Herpesvirus simiae (B virus) infection in clinical isolates from nonhuman primates. Isolates can be screened within 2-3 days from the time of collection of a specimen from a suspect lesion to final viral identification. Isolates were obtained from eight animals with suspected B virus infections. The results indicated the presence of B virus in each of the eight animals, each isolate unique from the others, but with the dominant prototypic pattern of the laboratory strain of B virus (E2490) and not HSV-1 (KOS), HSV-2 (186), or SA8 (3264).

Animals↗

PubMed1985

Development of molecular probes for simian herpesvirus detection.

A number of serologic procedures are available for specifically determining past infection due to H. hominis, or H. simiae (B virus). A herpesvirus isolated from primate tissues, however, does not lend itself to specific identification. Procedures currently in routine use simply do not provide an unequivocal identification of the isolate. We have previously demonstrated that H. simiae contain polypeptide and glycoprotein antigens distinct from those of other herpesviruses. At selected intervals, infected cells and controls were harvested after being both pulsed as well as continuously labelled from 4-24 hours post infection with 3H-glucosamine. 3H-mannose, and 3H-L-amino acid mixture. Between 40-45 infected cell polypeptides were observed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) with 7-11 glycoproteins noted. Analysis of the bands by electroblot utilizing anti-B virus sera showed the presence of eleven reactive bands within this molecular weight range from preparations in infected Vero and HEp-2 cell lines. Glucosamine labelled major glycoproteins migrated at 130K, 100K, 95K, 65K, 39K; mannose moieties migrated at 95K and 65K. SDS-PAGE profiles of B-virus when reacted with anti-gA/gB from HSV-1 and HSV-2 showed weak reactivities on the 125-130K complex. Anti-VP5 from HSV-1 failed to indicate any reactivity. Three polypeptides were revealed by SDS-hydroxylapatite analysis of the 130K complex with approximate molecular weights of 115K, 123K, and 130K; the 115K and 123K bands reacted with antisera prepared against gA/gB from HSV-1 and HSV-2, but not to anti-IgC or anti-2gC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗