猴嗜T淋巴白血病病毒研究进展

猴嗜T淋巴白血病病毒（simian T-cell lymphotropic virus,STLV）是非特定病原体（SPF）猴必须排除的病毒之一,是非人灵长类动物的一种重要的逆转录病毒,其潜伏期较长,非人灵长类动物感染了这一病毒在很长时间内无明显临床症状。目前,STLV已经遍布全球的非人灵长类,并可分为3种类型。研究证明STLV与非人灵长类动物的T淋巴白血病和淋巴肿瘤有关,其主要传播方式是通过血液传播。作者主要介绍了STLV的病毒学特点、流行及检测方法等的研究进展。     

Implications of simian retroviruses for captive primate population management and the occupational safety of primate handlers.

Nonhuman primates can be naturally infected with a plethora of viruses with zoonotic potential, including retroviruses. These simian viruses present risks to both captive nonhuman primate populations and persons exposed to nonhuman primates. Simian retroviruses, including simian immunodeficiency virus, simian type D retrovirus, simian T-lymphotropic virus, and gibbon ape leukemia virus, have been shown to cause clinical disease in nonhuman primates. In contrast, simian foamy virus, a retrovirus that is highly prevalent in most nonhuman primates, has not been associated with clinical disease in naturally infected primates. Although it has been shown that human retrovirus infections with human T-lymphotropic virus and human immunodeficiency virus originated through multiple independent introductions of simian retroviruses into human populations that then spread globally, little is known about the frequency of such zoonotic events. In this article, exogenous simian retroviruses are reviewed as a concern for zoo and wildlife veterinarians, primate handlers, other persons in direct contact with nonhuman primates, and other nonhuman primates in a collection. The health implications for individual animals as well as managed populations in zoos and research institutions are discussed, the cross-species transmission and zoonotic disease potential of simian retroviruses are described, and suggestions for working safely with nonhuman primates are provided.     

Variations in the immune response to herpesvirus saimiri in squirrel and rhesus monkeys

Humoral and cell-mediated immunity (CMI) to herpesvirus saimiri (HVS), an oncogenic lymphotropic herpesvirus, was studied in squirrel and rhesus monkeys. Natural antibody to HVS was found in five of six squirrel monkeys but there was no evidence of specific CMI directed against HVS. Rhesus monkeys did not show natural antibody or CMI against HVS antigens. Immunization with HVS, however, produced both antibody and specific CMI in the rhesus monkeys, but no CMI developed in the squirrel monkeys. These findings are important in the development of animal models for the treatment of tumors associated with lymphotropic herpesviruses.     

Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (Macaca mulatta)

Multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus macaque (Macaca mulatta) experimentally infected with simian immunodeficiency virus, strain SIVsmE660, and CD4+ T cell depleted. The animal was negative for simian retroviruses, SRV-1, -2, and -5. Polymerase chain reaction analysis of DNA from tumor and spleen tissue revealed abundant, preferential presence of retroperitoneal fibromatosis herpesvirus, the macaque homologue of the Kaposi sarcoma-associated herpesvirus (human herpesvirus-8), in the tumors. This was corroborated by demonstration of viral latent nuclear antigen-1 in the nuclei of a majority of the spindeloid tumor cells. Low levels of an additional macaque herpesvirus, rhesus rhadinovirus, were also detected in the spleen and tumor tissues. The spindeloid cells labeled positively for vimentin and CD117 but were negative for CD31, CD68, desmin, and smooth muscle cell actin. Collectively, these findings suggest a relation to but not absolute identity with simian mesenchymoproliferative disorders (MPD) or typical gastrointestinal stromal tumors (GISTs).     

ENDOMETRIOSIS AND A PARAOVARIAN CYST IN A RHESUS MACAQUE

We describe endometriosis in an aged rhesus macaque. There was a large mass and a related paraovarian cyst, typical of the disease. Endometriosis is a common finding in nonhuman primate. In this report, we also review the pathophysiology of the disease and summarize the historical and more recent relevant literature. Given the frequency of endometriosis in the rhesus monkey and the long-life spans (15-30 years) of nonhuman primates in captivity, endometriosis should be suspected in animals displaying the earliest signs of the disease: anorexia, dysmenorrhea, menorrhagia, irregular menstrual cycles, or infertility. Despite recent advances in the diagnosis and therapeutic strategies for endometriosis in women, the disease remains a significant cause of morbidity and ultimately, a cause of mortality, in the older nonhuman primate.     

NONHUMAN PRIMATE EXCRETORY UROGRAPHY*

Survey radiographs have not accurately identified renal contour or location in nonhuman primates. Excretory urography using 786 to 1193 mg iodinelkg body weight resulted in dense opacification of the renal parenchyma and pelvis. Abdominal compression improved visu- alization of the renal pelvis. Interpretation of the nonhuman primate excretory urogram was compromised by several anatomic characteristics of this animal group. Superimposition of the kidneys on the lateral radiograph limited evaluation of the renal contour. Since the renal pelvis in most species of nonhuman primates does not possess diverticula (as in the dog and cat) or a caliceal system (as in the pig and man), the diagnosis of pyelonephritis or renal mass lesions was difficult. Severe irregularities in the renal contour, size of the renal pelvis, or areas of deficient concentrating ability were identifiable in nonhuman primate excretory urograms, but the diagnosis of small cysts was not possible in smaller nonhuman primates. The presence of a caliceal collecting system in the spider monkey (Ateles sp.) suggests this animal as a potential model for the evaluation of human renal disease.     

Disseminated blastomycosis in a rhesus monkey (Macaca mulatta).

An 8-year-old male rhesus monkey (Macaca mulatta) died following a 6-day illness consisting of progressive depression, anorexia, labored abdominal breathing, coughing, and tachypnea. Gross necropsy findings included severe multifocal (miliary) granulomatous pneumonia, granulomatous splenitis, and multifocal cerebral abscesses. Histologic examination revealed 10-15-microm broad-based budding organisms within pyogranulomatous inflammatory lesions in the lung, tracheobronchial lymph node, brain, spleen, and liver. The distribution of extrapulmonary lesions was intermediate between that described for dogs and that described for humans. These findings were consistent with blastomycosis, which is previously unreported in nonhuman primates.     

Fatal herpesvirus infection in patas monkeys and a black and white colobus monkey

Fatal herpesvirus infections were diagnosed in 3 patas monkeys and 1 black and white colobus monkey over a 4-week period. Herpesvirus was isolated from 1 patas monkey and from the black and white colobus monkey. Both isolates had growth characteristics similar to Herpesvirus hominis and Herpesvirus simiae. The isolate from the colobus monkey antigenically appeared to be H simiae or H simiae-like, whereas the isolate from the patas monkey could not be conclusively identified with the antisera used. All affected animals were housed in close proximity to rhesus monkeys, the carrier host of H simiae.     

A comparative study of natural killer cell activity, lymphoproliferation, and cell phenotypes in nonhuman primates.

Three different species of nonhuman primates (baboons [Papio hamadryas], rhesus monkeys [Macaca mulatta], and African green monkeys [Cercopithecus aethiops]) were evaluated for their natural killer cell activity, and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin, and pokeweed mitogen) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Rhesus monkeys displayed the highest natural killer cell cytotoxic activity (185.7 +/- 33 lytic units) compared with those of baboons (83.8 +/- 19 lytic units) and of African green monkeys from West Africa (39.08 +/- 8 lytic units) and from the Caribbean basin (37.9 +/- 9 lytic units). No correlation was observed between the natural killer cell cytotoxic activity and the percentage of CD16+ natural killer cells among the three species studied. High spontaneous proliferative capacity was observed in African green monkeys obtained from West Africa compared with those of the other species studied. Although no significant differences were noted in T and B cell mitogen-induced in vitro proliferation, baboon mononuclear cells were less responsive to concanavalin A (stimulation index of 16 +/- 3 [mean +/- standard error of mean]) than to phytohemagglutinin (stimulation index of 47 +/- 12). However, rhesus and African green monkey cells proliferated more efficiently in response to concanavalin A. Unlike in human beings where the ratio between helper-inducer (CD4+) and cytotoxic-suppressor (CD8+) T-lymphocytes is generally greater than 1, the CD4+/CD8+ ratios in baboons and rhesus and African green monkeys were 0.58, 0.69, and 0.35, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serological responses to the cell associated herpesvirus and the manx calicivirus of SPF male cats with herpesvirus-induced urolithiasis

The feline cell associated herpesvirus (CAHV), but not the Manx calicivirus, was previously reported to induce urolithiasis in specific pathogen free (SPF) cats. Serum neutralization (SN) antibody studies, reported here, revealed that the experimental SPF cats did not have SN antibodies either against the CAHV or the Manx calicivirus in preinoculation serum samples. However, all cats inoculated with the CAHV (either alone or in combination with the Manx virus) developed SN antibodies against the herpesvirus. SN antibodies against the CAHV were detected 21 days post inoculation (PI) in 7 cats, 41 days PI in 4 cats, and 89 days PI in 1 cat. Cats inoculated with the Manx calicivirus alone, or in combination with the CAHV developed SN antibodies against the calicivirus in 7 to 21 days PI with that virus.     

A serological survey of cattle in the Thames-Coromandel district of New Zealand for antibodies to Ross River virus

AIM: To determine if cattle exposed to the southern saltmarsh mosquito (SSM), Aedes camptorhynchus, in the Thames-Coromandel district of New Zealand had been exposed to Ross River virus (RRV).

METHODS: A purposive sampling design was used to test cattle from seven farms located in close proximity to four sites infested with A. camptorhynchus in the Thames-Coromandel district. Sera from 207 cattle were tested for antibodies to RRV, using an ELISA and confi rmatory virus neutralisation test (VNT) as the gold standard.

RESULTS: All 207 cattle tested negative for antibodies to RRV using the ELISA and VNT.

CONCLUSIONS: This study found no evidence of exposure to RRV in cattle in locations in the Thames-Coromandel district of New Zealand where populations of SSM were present.     

A simple, rapid syncytial-inhibition test for antibodies to bovine leukemia virus.

Cocultivation of equal numbers of cells from a fetal lamb kidney line infected with bovine leukemia virus and African green monkey (Vero) cells results in the rapid production of syncytia. The effect was blocked or inhibited by serum containing antibodies to bovine leukemia virus. A serological test based on syncytial inhibition was compared to the agar gel immunodiffusion test and the modified direct complement fixation test for the detection of bovine leukemia virus antibodies in sera from leukosis-free cattle, cases of adult enzootic bovine lymphosarcoma and cattle from herds in contact with enzootic lymphosarcoma. The results showed the syncytial inhibition test to react positively with sera from all cases of adult enzootic lymphosarcoma, but to be much less sensitive than the other tests in detecting bovine leukemia virus antibodies in sera of exposed animals.     

The alcelaphine herpesvirus-1 ORF 57 encodes a nuclear shuttling protein

Alcelaphine herpesvirus-1 (AlHV-1) is a γ₂ rhadinovirus associated with Malignant Catarrhal Fever (MCF) in cattle. ORF 57 is well conserved among gammaherpesviruses and it has been shown that the ORF 57 gene products of Herpesvirus Saimiri (HVS), Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) play an important role in regulating viral gene expression. The AlHV-1 ORF 57 gene product has not been characterized. In the accompanying paper we have demonstrated that AlHV-1 ORF 57 encodes an immediate early protein that acts as a regulator of gene expression. The ORF 57 gene product has an up-regulatory effect only on another immediate early gene product encoded by ORF 50. Here we show that the ORF 57 gene product is a nuclear protein. When ORF 57 was fused to the gene encoding Enhanced Green Fluorescent Protein (EGFP), the fusion protein exhibited a punctate nuclear distribution that co-localized with the nucleolar phosphoprotein C23. The nuclear localisation signal of ORF 57 gene product was located at the N-terminus. The ORF 57 gene product travels from nucleus to the cytoplasm, where it accumulates during Actinomycin D treatment. The domain involved in nuclear shuttling was also localised at the N-terminal region of the protein. Thus in common with homologues in other herpesviruses the AlHV-1 ORF 57 gene product is a nuclear cytoplasmic shuttling protein which may play a role in export of viral mRNAs from the nucleus of infected cells.     

BV147感染Vero细胞的超微结构

应用电镜对1997年本实验室从野外捕获的恒河猴分离的BV147在Vero细胞上的形态发生和增殖规律进行了观察。结果表明，新分离为BV147是疱疹病毒属成员，在细胞核内复制、增殖，在核内膜以“出芽方式”获得囊膜而达到成熟，通过细胞的胞吐或胞系统排到细胞外，接毒后18h病毒主要在核内，24h则可在核膜间隙、胞浆和细胞外见到大量成熟病毒颗粒。     

Studies concerning etiology of sheep-associated malignant catarrhal fever in Europe.

The etiological agent of sheep-associated malignant catarrhal fever (MCF) in Europe has not been isolated directly from sheep. The occurrence of antibodies against the African bovine herpesvirus (BHV-3, WC 11) in cattle and sheep was examined using recently modified indirect immunofluorescence test (IIFT) and neutralization test (NT) methods. Studies revealed that sheep and cattle sera in Europe were free from neutralizing antibodies of BHV-3. The IIFT could not establish the presence of antibodies to African BHV-3 in cattle but revealed that about 22.4% of sheep sera reacted to it. Apart from the well known ovine herpesvirus (BHV-5), occurrence of another herpesvirus in Europe had been expected. This virus is not identical with the WC 11 strain, but it is in antigenic relationship to it. We had for the first time substantial serological evidence to the effect that sheep-associated MCF in Europe is a herpesvirus related to the African strain.     

Pathogenesis of gammaherpesvirus infections

Gammaherpesviruses are members of an emerging subfamily among the Herpesviridae. Two genera are discriminated: (i) lymphocryptovirus, including its type species Epstein-Barr virus (EBV), and (ii) rhadinovirus, including viruses of interest for medicine, veterinary medicine, and biomedical research, i.e. alcelaphine herpesvirus 1, bovine herpesvirus 4, equine herpesvirus 2, human herpesvirus 8, mouse herpesvirus 68, and ovine herpesvirus 2 (OvHV-2). The perception that these viruses have a narrow host range is misleading, since they cover a surprisingly wide host range, both on the cellular and the organism's level. For example, the natural range of OvHV-2 infection extends over a common animal order. While the host range determinants of EBV are well known, the corresponding features of the rhadinoviruses need still to be defined. Similarly, the gene expression patterns of the veterinary rhadinoviruses during latency require further characterization. In vivo, the gammaherpesviruses have evolved to actively protect their latently infected cells from being destroyed by immune functions of their native host. In return, those reservoir hosts have evolved to being infected and transmit the virus without overt disease symptoms. However, a balanced immune response needs to be in control over the number of infected cells. Virus excretion is usually at low level and may occur either constantly or intermittently. Animal species that are targeted by the virus but did not participate in the process of co-evolution as well as hosts with immune deficiencies are known to loose control over the amount of latently infected cells, which results in the development of lethal diseases, such as malignant catarrhal fever or Kaposi's sarcoma.     

Bovid herpesvirus 2 latency: failure to recover virus from central sensory nerve ganglia.

Latent bovid herpesvirus 2 was sought in sensory ganglia, epithelium and lymph nodes from cattle having antibodies against bovid herpes virus 2. Tissues from eight animals were maintained in vitro as explants for 49-72 days during which all expended media was tested for virus. Three animals were pretreated with corticosteroids prior to slaughter. Infectious bovine rhinotracheitis virus was recovered from one animal, but bovid herpesvirus 2 was not detected.     

A spontaneous uterine sarcoma in a rhesus monkey (Macaca mulatta)

In primates, little has been reported about malignant mesenchymal uterine tumours. A case of a spontaneous metastasising uterine sarcoma in a 17-year-old rhesus monkey is presented. Clinically, transient abdominal pain, spasms, nausea, anaemia, a firm uterus and bloody vaginal discharge were noted. In a diagnostic laparoscopy, both massive adhesions in the lesser pelvis and 10 ml of ascites fluid were detected. In necropsy, in addition to peritonitis with massive adhesions, a cauliflower-shaped, irregular, tough, greyish-white uterine tumour was seen. Two cherry-sized tumour metastases were noticed in the greater omentum. In histology, both in the uterus and the metastases, a sarcoma with a low amount of connective tissue and well-differentiated cell nuclei was identified.     

Congenital cystic adenomatoid-like malformation in a cynomolgus monkey (Macaca fascicularis)

Congenital cystic adenomatoid malformation (CCAM) is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature, ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts. Although various clinical and pathologic studies of CCAM in humans exist, CCAM has yet to be reported in animals, even in nonhuman primates. In the present study, histopathologic analyses of a neonatal cynomolgus monkey that died 17 days after birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epithelium. The epithelium projected a few ciliates into the air spaces and produced mucus. To our knowledge, this is the first case study describing CCAM or a CCAM-like lesion in nonhuman primates.