Pathology of ovine adenovirus type 4 infection in SPF lambs: pulmonary and hepatic lesions.

Seven lambs were challenged with an aerosol of OA4 virus. Four developed mild pulmonary oedema and a sparse accumulation of mononuclear cells around blood vessels similar to results reported previously. In addition, three had focal hepatic necrosis and one of these three had a non-suppurative occlusive cholangitis and portal tract lymphangitis and thrombosis. Basophilic intranuclear IB's were identified in many necrotic hepatocytes, in lymphatic endothelial cells involved in thrombi but in only one bile duct epithelial cell. Ultrastructurally, virions with the characteristics of adenovirus were seen in hepatocytes. Although only one IB was seen in the affected biliary system there was no evidence that it was caused by an agent other than OA4. Virus was considered to infect the respiratory system directly, be swallowed to infect the alimentary system and carried, possibly within cells, via a haematogeneous and/or lymphogenous route to the liver. The effect of naturally acquired virus on sheep is unknown but it is possible that it may predispose the host to more serious infections.     

Experimental infection of specific pathogen-free New Zealand White rabbits with five strains of amyxomatous myxoma virus.

Myxomatosis is a specific disease of the European rabbit (Oryctolagus cuniculus) due to a virus belonging to the genus Leporipoxvirus. Forty-seven years after its deliberate introduction into Europe, the clinical aspects and the epizootiology of myxomatosis have changed. Two forms (nodular and amyxomatous) of the disease have been identified to date. A comparative study was made of the clinical signs, pathogenesis and gross lesions observed in male specific pathogen-free New Zealand White rabbits inoculated with five strains of amyxomatous myxoma virus. All five strains induced the characteristic amyxomatous myxomatosis clinical syndrome with clinical signs that differed only in intensity. The varying clinical intensity, together with the results of virological examination question the virulence of at least three of the five strains. Genomic analysis confirmed that the five strains came from the Lausanne strain introduced in 1952 in France and not from an unnoticed introduction of a Californian strain of myxoma virus. No link was found between the amyxomatous myxoma virus strains and the SG33 vaccine strain. 1999 Harcourt Publishers Ltd.     

Experimental rotavirus infection in lambs.

Inoculation of lamb rotavirus to gnotobiotic lambs produced a disease characterized by diarrhoea and anorexia. Rotavirus was excreted in the faeces of the lambs for several days. One-day-old lambs were more susceptible than 12-day-old lambs.A serological response to infection was detected in all lambs by complement fixation and immunofluorescence techniques, using antigens prepared from calf rotavirus. Lamb rotavirus antiserum did not neutralize calf rotavirus, indicating the distinct nature of the lamb rotavirus.No evidence of latent infections was detected by treating the lambs with an immunosuppressant four months after initial recovery.     

A sixth species of ovine adenovirus isolated from lambs in New Zealand

Summary Two adenoviruses (WV 419/75 and WV 757/75), isolated from lambs in New Zealand were compared using neutralisation tests with the five recognised ovine adenovirus species, NINE bovine and four porcine adenoviruses. WV 419/75 did not cross-react with any of the viruses tested and represents a new ovine adenovirus species (OAV-6). WV 757/75 cross-reacted with bovine adenovirus type 7 (BAV-7) with a homologous to heterologous titre ratio of 16 in one direction only, and also showed a substantial one-way cross reaction in haemagglutination-inhibition tests (WV 757 antiserum inhibiting haemagglutination by BAV-7). There was therefore insufficient distinction from BAV-7 virus to allow designation as a separate species.Fluorescent antibody studies with WV 419 and WV 757 demonstrated virus inclusions in the nuclei of infected cells. These were stained by antiserum to OAV-4 indicating presence of the mammalian group antigen.Thin section electron microscope studies showed typical adenovirus particles and associated inclusions in cell nuclei. The similarity of the two viruses to the bovine subgroup 2 adenoviruses in several of their properties is discussed.With 2 Figures     

Persistent infection of Muntiacus muntjak cells with adenovirus type 2 and abortive infection with adenovirus type 12

The Indian deer Muntiacus muntjak has the lowest chromosome number reported for mammals, six for the female and seven for the male animal. Adenovirus type 2 (Ad2) can replicate efficiently in these cells. When inoculated at low multiplicity, however, Ad2 establishes a persistent infection. The viral DNA persists in these cells apparently in a free form and replicates continuously. Tests for viral antigens and infectious center assays have revealed that about 1 to 2% of the cells produce Ad2. The persistent infection can be abolished by treating the infected cells with rabbit anti-Ad2 serum. As shown by the Southern blotting technique, the viral DNA is lost from the cells which were cured by antiserum treatment. Judging from the unabated replication of Sindbis virus or vesicular stomatitis virus in persistently Ad2-infected Muntiacus muntjak (M.m.) cells, the persistence of Ad2 is not accompanied by the production of interferon. Nor is there evidence for an Ad2-specific inhibitory factor, since persistently infected cells can be superinfected with high multiplicities of Ad2. Adenovirus type 12 (Ad 12) cannot multiply in M.m. cells. A very low level of replication of unit length Ad12 DNA can be detected. M.m. cells abortively infected with Ad12 continue to grow, and the viral DNA is eventually lost from the bulk of the cells. Ad12 infection leads to chromosomal abnormalities in M.m. cells. At 24 hr postinfection, 30–40% of the cells could be shown to be T antigen positive by immune fluorescence.     

Evidence of hepatitis E virus infection in specific pathogen-free rabbits in Korea

Rabbits are considered a new natural reservoir of hepatitis E virus (HEV). In this study, HEV infection was verified by the detection of partial genomic sequence of HEV and anti-HEV antibodies in specific pathogen-free (SPF) rabbits. HEV RNA was found in 6.4% serum and 13.5% fecal samples from 126 SPF rabbits. Anti-HEV antibodies were also detected in 4.0% of the SPF rabbits. HEV genetic sequences isolated from the rabbits were clustered into a rabbit HEV clade with other rabbit HEV isolates; they were found to be most closely related with a rabbit HEV sequence previously reported in Korea. Therefore, HEV infection should be diagnosed before conducting experiments involving SPF rabbits.     

Fatal adenovirus infection associated with new genome type

The first fatal case caused by the new genome type 7i is described in an 8-month-old boy requiring long-term respiratory support who developed Reye's syndrome, acute respiratory distress, and bronchiolitis obliterans with fatal evolution. Adenovirus was detected in nasopharyngeal secretions and was persistently positive during hospitalization. IgM and IgG adenovirus antibody titers measured in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively. Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL-2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-α, 35 pg/ml, IL-1 and IL-4 undetectable, IFN-α 2,200 pg/ml, and IFN-γ 700 pg/ml. Virologic studies showed that adenovirus isolated belonged to subgenus B, and digestion of viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse alveolar damage and perivenular fatty degeneration with polymorphonuclear infiltrates in the periportal spaces. The difficulty in obtaining adequate oxygenation with minimization of iatrogenic oxygen injury is discussed.J. Med. Virol. 54:233–236, 1998. © 1998 Wiley-Liss, Inc.     

Experimental infection with mouse adenovirus in adult mice

Summary Intraperitoneal inoculation of adult mice with mouse adenovirus caused a generalized infection with occasional deaths. Virus was found widely distributed in several tissues as well as in white blood cells from the third day after inoculation. L cells were used for viral recovery and assay. The highest viral titers were reached in the spleen. No virus was detected in tissues and white blood cells after 2 weeks. In contrast, virus was demonstrated in the urine by the 14th day and viruria persisted for as long as 2 years. A similar picture was found after intranasal inoculation. The failure to demonstrate virus in tissues after the early weeks of infection was probably due to the production of high levels of antibody for up to 2 years.     

Acute-phase proteins and hematologic values in ovine lentivirus-infected lambs treated with recombinant ovine IFN-tau.

To evaluate changes in complete blood cell (CBC) counts, haptoglobin and fibrinogen in ovine lentivirus (OvLV)-infected lambs treated with recombinant ovine interferon-tau (rOVIFN-tau), 24 lambs were allocated to one of four groups (n = 6 per group): (1) virus + rOvIFN-tau, VI, (2) virus + placebo, VP, (3) no virus + rOVIFN-tau, NVI, and (4) no virus + placebo, NVP. Three lambs in each group were treated once a day for 12 weeks, and the remaining 3 lambs were treated for 33 weeks. Blood was collected at days 0, 7, and 10 and at weeks 2-10, 12, 32, and 33 to determine CBC counts, as well as haptoglobin and fibrinogen levels. Hematologic values remained within normal limits in all groups. However, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and packed cell volume (PCV) values decreased (p < 0.05) in the two rOvIFN-tau-treated groups (VI and NVI) compared with the placebo-treated (VP and NVP) groups. Both rOvIFN-upsilon and OvLV had a mild negative effect on neutrophil numbers. Although Hb, MCV, MCHC, PCV, and neutrophil values declined in the rOvIFN-tau-treated lambs compared with the placebo-treated lambs, these values remained within the reference range for sheep. Experimental lambs did not show adverse clinical signs associated with OvLV infection or as a result of rOvIFN-tau treatment. The lack of significant side effects of high-dose rOvIFN-tau in sheep and previous reports of broad-spectrum and cross-species antiviral activity suggest that rOvIFN-tau warrants further investigation as an antiviral therapeutic agent.     

Experimental infection of egg-laying hens with Salmonella enteritidis phage type 4

Chickens were inoculated intravenously with 10(5) or 10(6) organisms. Heavy infection of the ovaries occurred and some infection persisted in this organ for several weeks. Most of the ovarian infections were confined to the interstitial tissues and not to the yolk contained in the large follicles. Infections of the ovary did not result from contamination from infected air sacs. None of 810 eggs laid contained S. enteritidis. Chickens infected orally gave similar results to those following intravenous inoculation although the number of isolations obtained from the caeca and cloaca were higher. S. enteritidis was isolated from two of 633 eggs in which the contents only were cultured and from 36 of 614 eggs in which both shell and contents were cultured. The serum IgG response to oral inoculation was monitored by an ELISA using a whole cell sonicate or lipopolysaccharide antigen. High titres of IgG were detected for 27 weeks after infection when the experiment was terminated. The experiments suggest that most infected eggs laid by 5. enteritidis-infected hens are surface-contaminated and do not result from infected ovaries.     

Multi-centric histiocytosis: Experimental induction in broiler and specific pathogen-free leghorn chickens

Seventy-five 3-day-old broiler chicks and twenty specific pathogen-free leghorn chicks were injected with 0.5 ml of a homogenate, prepared from organs from broilers diagnosed with naturally-occurring multicentric histiocytosis (MH). Equal numbers of uninjected broiler and leghorn chicks (controls) were maintained in adjacent pens. Ten weeks later, nine broilers had well-developed gross and microscopic MH lesions. The distribution and histological appearance of lesions in these experimental chicks was similar to lesions described in naturally occurring field cases. Six leghorns had gross lesions similar to those found in their broiler counterparts; however, in the leghorns, the cellular masses contained more lymphocytes and, additionally, masses were found in the gizzard musculature. One gizzard contained a sarcoma. Broiler chickens with MH weighed less than their control counterparts and were more likely to be anaemic. Sequences specific for reticuloendotheliosis viruses (REV) were found in the MH homogenate, in organs from most affected experimental leghorns and broilers, and in organs from a control broiler. However, REV were not isolated from these tissues, nor were specific antibodies for REV or avian leukosis/sarcoma viruses (ALV) found in chick serum. Leukosis/sarcoma viruses were isolated from some MH-affected experimental leghorns and broilers. Sequences specific for Marek's disease herpesvirus were not identified by polymerase chain reaction. The aetiology of MH remains unknown.     

Ribosomal RNA synthesis after infection with adenovirus type 2

The synthesis of mature cytoplasmic ribosomal RNA was preferentially inhibited in comparison to 4S RNA in T6a (hamster) cells infected with adenovirus type 2, but not in uninfected controls. No effect was observed in 3T3–4E (mouse) cells infected with adenovirus type 2. When T6a-3T3-4E hybrids were infected with this virus, no significant change in the proportion of hamster and mouse cytoplasmic ribosomal RNA synthesized was detected, in comparison to uninfected hybrid cells.