Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of ß2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.

Intestinal epithelial barrier disruption through altered mucosal microRNA expression in human immunodeficiency virus and simian immunodeficiency virus infections.

UNLABELLED: Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4(+) T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5'-3'-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE: MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of miRNA biogenesis machinery during infection. These findings suggest that the disruption of miRNA in the small intestine likely plays a role in intestinal enteropathy during HIV infection.

The oral and conjunctival microbiotas in cats with and without feline immunodeficiency virus infection.

The oral and conjunctival microbiotas likely play important roles in protection from opportunistic infections, while also being the source of potential pathogens. Yet, there has been limited investigation in cats, and the impact of comorbidities such as feline immunodeficiency virus (FIV) infection has not been reported. Oral and conjunctival swabs were collected from cats with FIV infection and FIV-uninfected controls, and subjected to 16S rRNA gene (V4) PCR and next generation sequencing. 9,249 OTUs were identified from conjunctival swabs, yet the most common 20 (0.22%) OTUs accounted for 76% of sequences. The two most abundant OTUs both belonged to Staphylococcus, and accounted for 37% of sequences. Cats with FIV infection had significantly lower relative abundances of Verrucomicrobia, Fibrobacteres, Spirochaetes, Bacteroidetes and Tenericutes, and a higher relative abundance of Deinococcus-Thermus. There were significant differences in both community membership (P = 0.006) and community structure (P = 0.02) between FIV-infected and FIV-uninfected cats. FIV-infected cats had significantly higher relative abundances of Fusobacteria and Actinobacteria in the oral cavity, and significantly higher relative abundances of several bacterial classes including Fusobacteria (0.022 vs 0.007, P = 0.006), Actinobacteria (0.017 vs 0.003, P = 0.003), Sphingobacteria (0.00015 vs 0.00003, P = 0.0013) and Flavobacteria (0.0073 vs 0.0034, P = 0.030). The feline conjunctival and oral microbiotas are complex polymicrobial communities but dominated by a limited number of genera. There is an apparent impact of FIV infection on various components of the microbiota, and assessment of the clinical relevance of these alterations in required.

Influence of small ruminant lentivirus infection on cheese yield in goats.

Three-year cohort study was carried out to investigate the influence of small ruminant lentivirus (SRLV) infection on cheese yield in goats. For this purpose records of milk yield, milk composition and cheese yield were collected in a dairy goat herd. Cheese yield was recorded as the amount of fresh cheese obtained from 1 kg milk. All goats were serologically tested for SRLV infection twice a year. The analysis included 247 records in total (71 for seropositive and 176 from seronegative individuals) and was carried out with the use of the four-level hierarchical linear model (α = 0·05). SRLV infection proved to be a statistically significant independent factor reducing cheese yield (P = 0·013)--when other covariates were held constant cheese yield was reduced by 4·6 g per each 1 kg milk in an infected goat compared with an uninfected goat. Other statistically significant covariates positively associated with cheese yield were protein contents, fat contents and the 3rd stage of lactation (P < 0·001 for all).

Twelve-year cohort study on the influence of caprine arthritis-encephalitis virus infection on milk yield and composition.

This long-term observational cohort study was carried out to evaluate the effect of caprine arthritis-encephalitis virus (CAEV) infection on the quantitative and qualitative characteristics of milk production in dairy goats. For this purpose, a dairy herd comprising both CAEV-infected and uninfected female goats was observed for 12 consecutive years. Records on daily milk yield, somatic cell count (SCC), and contents of the major milk components (fat, protein and lactose) were collected every month. In total, 3,042 records (1,114 from CAEV-positive and 1,928 from CAEV-negative animals) from 177 female goats were used for statistical analysis. The multi-trait repeatability test-day animal model using the derivative-free multivariate analysis package with the average information-REML method was applied to eliminate the influence of factors other than CAEV infection on milk production in goats. The statistical significance of the differences between estimates for seropositive and seronegative goats was evaluated using Student's t-test. The effect of age of goats (parity) on their serological status was also estimated with the one-trait repeatability test-day model. The serological status of goats was linked to parity: the higher the parity, the greater the probability of CAEV infection. No significant differences between infected and uninfected goats with respect to daily milk yield and SCC were found. On the other hand, the milk of uninfected goats contained more total protein (3.40% vs. 3.35%), fat (3.69% vs. 3.54%), and lactose (4.30% vs. 4.25%) than the milk of infected goats. Even though these differences were highly significant, they were small when expressed numerically.

The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis.

The vertebrate gut harbors a vast community of bacterial mutualists, the composition of which is modulated by the host immune system. Many gastrointestinal (GI) diseases are expected to be associated with disruptions of host-bacterial interactions, but relatively few comprehensive studies have been reported. We have used the rhesus macaque model to investigate forces shaping GI bacterial communities. We used DNA bar coding and pyrosequencing to characterize 141,000 sequences of 16S rRNA genes obtained from 100 uncultured GI bacterial samples, allowing quantitative analysis of community composition in health and disease. Microbial communities of macaques were distinct from those of mice and humans in both abundance and types of taxa present. The macaque communities differed among samples from intestinal mucosa, colonic contents, and stool, paralleling studies of humans. Communities also differed among animals, over time within individual animals, and between males and females. To investigate changes associated with disease, samples of colonic contents taken at necropsy were compared between healthy animals and animals with colitis and undergoing antibiotic therapy. Communities from diseased and healthy animals also differed significantly in composition. This work provides comprehensive data and improved methods for studying the role of commensal microbiota in macaque models of GI diseases and provides a model for the large-scale screening of the human gut microbiome.

Induction of immunosuppressive functions and NF-κB by FLIP in monocytes.

Immunosuppression is a hallmark of tumor progression, and treatments that inhibit or deplete monocytic myeloid-derived suppressive cells could promote anti-tumor immunity. c-FLIP is a central regulator of caspase-8-mediated apoptosis and necroptosis. Here we show that low-dose cytotoxic chemotherapy agents cause apoptosis linked to c-FLIP down-regulation selectively in monocytes. Enforced expression of c-FLIP or viral FLIP rescues monocytes from cytotoxicity and concurrently induces potent immunosuppressive activity, in T cell cultures and in vivo models of tumor progression and immunotherapy. FLIP-transduced human blood monocytes can suppress graft versus host disease. Neither expression of FLIP in granulocytes nor expression of other anti-apoptotic genes in monocytes conferred immunosuppression, suggesting that FLIP effects on immunosuppression are specific to monocytic lineage and distinct from death inhibition. Mechanistically, FLIP controls a broad transcriptional program, partially by NF-κB activation. Therefore, modulation of FLIP in monocytes offers a means to elicit or block immunosuppressive myeloid cells.

Viral gene expression and provirus load of Orf-A defective FIV in lymphoid tissues and lymphocyte subpopulations of neonatal cats during acute and chronic infections.

Neonatal cats were infected with a wild type (JSY3) or orf-A defective (JSY3DeltaORF-A) feline immunodeficiency virus (FIV) to determine the provirus load and level of viral gene expression at the acute versus chronic stages of infection. FIV DNA in the thymus, lymph node, peripheral blood mononuclear cells (PBMCs) and lymphocyte subpopulations at week 8 post-infection was lower in animals infected with JSY3DeltaORF-A as compared to that of JSY3. At week 16 we observed no significant difference in provirus load between the two groups except for B cells where it was higher in the JSY3 infection. In B cells proviral burden was found to be the same in animals infected with JSY3 for both time points. In the chronic stage, therefore, proviral burden dominates in B cells for JSY3, whereas the level of JSY3DeltaORF-A was lower with comparable values for all lymphocytes at both weeks 8 and 16. Gene expression profiles as measured by real time PCR for gag and rev transcripts revealed decreased levels of JSY3DeltaORF-A mRNAs as compared to that of JSY3. The JSY3 chronic phase infection showed viral gene expression to be higher in B cells relative to CD4+ and CD8+ cells. The presence of viral RNA in CD8 and B cells during the chronic infection implicates active virus replication. Hematological profiles revealed that there was a decline in the number of B cells in JSY3DeltaORF-A-infected cats during the chronic stage of infection while no significant change was observed in animals infected with the wild type virus. Comparative analysis of cell numbers to provirus load and levels of viral transcripts in CD4+ and CD8+, however, did not correlate cell numbers to the levels of viral DNA and gene expression. It remains to be determined whether the relatively high virus burden in B cells as compared to CD4+ and CD8+ cells reflects a role for Orf-A in a shift to B cell virus load during the chronic stage of FIV infection.

Characterization and role of lentivirus-associated host proteins.

Enveloped viruses obtain their envelopes during the process of budding from infected cells. During this process, however, these viruses acquire parts of the host cell membranes and host cell-derived proteins as integral parts of their mature envelopes. These host-derived components of viral envelopes may subsequently exhibit various effects on the life cycle of the virus; virus cell interactions, especially host response to virus-incorporated self-proteins; and the pathogenesis of the disease induced by these viruses. Although it was known for some time that various viruses incorporate host cell-derived proteins, the issue of the role of these proteins has received increased attention, specifically in connection with human immunodeficiency virus (HIV) infection and development of acquired immunodeficiency syndrome (AIDS) in humans. The aim of this review is to summarize our current knowledge of the analysis and role of host-derived proteins associated with enveloped viruses, with emphasis on the potential role of these proteins in the pathogenesis of AIDS. Clearly, differences in the clinical outcome of those nonhuman primates infected with simian immunodeficiency virus (SIV) that are disease resistant compared with SIV-infected species that are disease susceptible provide a unique opportunity to determine whether differences in the incorporation of distinct sets of host proteins play a role with distinct clinical outcomes.

Characteristics of ovine and caprine lentivirus infections.

A majority of ovine lentivirus (OvLv) infections seen on farms develop after long incubation and a slow progression of disease to death but in nature they may also have short latency and cause acute leukoencephalitis and/or acute arthritis and pneumonia in young kids or lambs with exceptionally high mortality. Histopathologically, OvLv diseases may be characterized by lymphoid infiltration, lymphoid hyperplasia with germinal centers and plasmocytosis in the lungs and/or in the CNS, joints and udder. Lymphoid hyperplasia in lymph nodes and spleen, as well as lymphoid infiltration in the kidneys, are almost always seen in advanced cases. In some cases, it shows similarities to lymphoproliferative diseases that are considered malignant. Alveolar epithelial hyperplasia in the lungs is generally also seen, especially in older goats with caprine arthritis encephalitis virus (CAEV), and proliferation of these epithelial cells may form acine and papillary structures and in some cases are histopathologically indistinguishable from tumor nodules seen in sheep pulmonary adenomatosis. Because of complexities in the host-lentovirus interaction, cell-associated transmission and extensive antigenic and genomic variation among infecting isolates, control of infection or prevention of spread are problematic by traditional methods and exploration of alternative control strategies employing selection and expansion of animals genetically resistant to OvLv or transgenic for certain viral genes, merits consideration. Interestingly, the pure Awassi sheep breed are susceptible to infection but do not develop the disease, as do European breeds or cross-breeds in Israel, ie they are infected but not diseased. It seems that the local Bedouin black goat breed is resistant to infection of CAEV under natural conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of early and late feline immunodeficiency virus encephalopathies.

DESIGN: The study of the early and late stages of encephalopathy following infection by the feline immunodeficiency virus (FIV) was carried out with laboratory and naturally infected cats. INTERVENTIONS: Animals infected experimentally were injected with three different isolates of the virus, administered either intracerebrally or intravenously, and sacrificed at 7 days, 1 and 6 months (intracerebral injection), and 2, 6 and 12 months (intravenous injection) post-inoculation, respectively. CONCLUSIONS: General features of encephalopathy were found to be identical, regardless of the method of inoculation or the viral strain used. Moderate gliosis and glial nodules, sometimes associated with perivascular infiltrates and white matter pallor, were observed at 1 month (intracerebral injection) and 2 months (intravenous injection), and remained unchanged until 12 months post-inoculation. The fact that these initial stages are identical for intravenously and intracerebrally inoculated cats suggests that the virus enters the brain very quickly in intravenously infected animals. Encephalopathy in cats naturally infected with FIV only consisted of gliosis, glial nodules, white matter pallor, meningeal perivascular calcification and meningitis. These lesions were more frequent and more severe in the group coinfected with feline leukaemia virus and feline infectious peritonitis virus. Although multinucleated cells were rare, the strong similarities between HIV and simian immunodeficiency virus encephalopathies at comparable stages support the view that FIV infection may represent an interesting model for a physiopathological approach of HIV infection of the central nervous system.

Phenotypic and ultrastructural characteristics of bronchoalveolar lavage cells of lentivirus-infected lambs treated with recombinant ovine IFN-tau.

Ovine lentivirus (OvLV) belongs to the family Retroviridae and closely resembles the human immunodeficiency virus (HIV). Pulmonary lesions in OvLV-infected sheep consist of lymphoid interstitial pneumonia (LIP) and lymphocytic alveolitis. Similar pulmonary lesions occur in up to 40% of HIV-infected children and in some adults with AIDS. Interferon-tau (IFN-tau), a type I IFN, is produced by trophectoderm of ruminant conceptuses and is the pregnancy recognition signal in these species. To evaluate changes in phenotypes of bronchoalveolar lavage (BAL) cells of OvLV-infected lambs treated with recombinant ovine IFN-tau (rOvIFN-tau), 24 lambs were randomly allocated to one of four groups (n = 6 per group): 1, no virus + placebo (NVP); 2, no virus + rOvIFN-tau (NVI); 3, virus + placebo (VP); 4, virus + rOvIFN-tau (VI). The BAL cells from 3 lambs in each group were labeled with monoclonal antibodies (mAb) to cell surface markers at 16 weeks of treatment, and cells from the remaining 3 lambs in each group were labeled with mAb at 34 weeks of treatment. After labeling, BAL cells were analyzed by flow cytometry. The morphology of BAL cells from all experimental lambs was examined by transmission electron microscopy (TEM). At week 16, no differences in the relative proportions of BAL cell phenotypes were detected among the experimental groups. At week 34, VI lambs had higher proportions of CD8(+), gammadelta(+), MHC class II(+), and L-selectin (LS(+)) BAL cells compared with VP lambs. Higher proportions of CD14(+) and CD44(+) cells were found in VP lambs compared with NVP lambs at 34 weeks. OvLV-like particles were detected only in bronchoalveolar macrophages of VP lambs. In this study, rOvIFN-tau increased the proportions of primary antiviral gammadelta(+) and CD8(+) immune cells in OvLV-infected lambs. This may represent a cellular mechanism to explain the antiviral and therapeutic efficacy of this cytokine, in addition to its direct antiviral effect. However, because the actual number of cells labeled with mAb CD8 was low and some subsets of gammadelta cells may coexpress the CD8 marker, further studies are necessary to better define the role of rOvIFN-tau in the modulation of these cells in vivo.

Detection of genetic diversity among bovine immunodeficiency virus population by single-strand conformation polymorphism analysis.

Serial virus specimens rescued from rabbits, experimentally infected with bovine immunodeficiency (BIV) strain R29, were monitored for changes in quasispecies population, using the single-strand conformation polymorphism (SSCP) analysis. The generation of characteristic SSCP patterns enables the rapid differentiation of BIV variants derived from the conserved part on the env region of the BIV genome, reducing the need for expensive and time-consuming direct sequencing analyses. Our results showed genetic polymorphism among a number of sampled BIV population in experimentally infected rabbits. At least three SSCP patterns (BIV quasispecies) were detected. The SSCP analysis allows for an easy, sensitive, and rapid screening of genetic variants of the virus and the assessment of variation at a number of tissue target sites. These variations may relate to cell-type targets and/or disease progression, and could be significant to our understanding of lentiviral pathogenesis.

Feline immunodeficiency virus infection of cats as a model to test the effect of certain in vitro selection pressures on the infectivity and virulence of resultant lentivirus variants.

Three groups of specific pathogen-free (SPF) domestic cats, each containing 5 animals, were infected with one of three closely related FIV variants and monitored for 36 weeks. A fourth group of 5 cats was sham-infected and served as uninfected controls. FIV variants included: (1) a fully virulent animal passaged FIV-Petaluma; (2) a Crandell feline kidney (CrFK) cell-adapted FIV-Petaluma (FIV-CrFK); and (3) a variant of FIV-CrFK (FIV-CrFKAZT) that had been selected in vitro for resistance to azidothymidine. Cats infected with fully virulent FIV-Petaluma strongly seroconverted, became persistently viremic, and exhibited lymphadenopathy, neutropenia, and inversion of the CD4+:CD8+ T cell ratio. Cats infected with FIV-CrFK seroconverted but the antibody responses were much weaker and more variable; two of the cats became transiently viremic and no hematologic abnormalities or clinical signs of illness other than a very mild lymphadenopathy were observed. None of the five cats inoculated with FIV-CrFKAZT seroconverted, became viremic, or exhibited any gross or hematologic signs of disease, even though proviral DNA was transiently detected in tissue following inoculation. This study demonstrates that the FIV infection model can be used to assess differences in the virulence of FIV variants, including variants selected for antiretroviral drug resistance.

Recent advances in the understanding of Jembrana disease.

Jembrana disease is a severe and acute clinical disease in Bali (Bos javanicus) cattle with a case fatality rate of about 20%, and a mild sometimes subclinical disease in other cattle types and buffalo. The aetiological agent has been identified as a lentivirus, designated as Jembrana disease virus (JDV). Preliminary sequence analysis has confirmed the identity of JDV as a lentivirus and has shown that it is distinguishable from BIV. There is antigenic cross-reactivity between the capsid protein of JDV and the previously identified bovine lentivirus designated bovine immunodeficiency virus (BIV). Serological tests that detect antibody to the capsid protein of JDV or BIV would not differentiate between antibody due to infection by either virus. The diseases induced by BIV and JDV infection in cattle are very different, and the pathogenesis of JDV infection in Bali cattle is unusual for a lentivirus infection.

Monocyte function in cattle experimentally infected with bovine immunodeficiency-like virus.

The effects of bovine immunodeficiency-like virus (BIV) on monocyte function were examined in experimentally infected cattle and in monocytes infected in vitro. Infection with the R29 isolate of BIV appeared to have relatively little effect on monocyte function in cattle during the first 2 years postinfection (PI). For the first 4 to 8 months post infection, monocyte phagocytosis of Staphylococcus aureus tended to be lower (P = 0.06) in BIV infected calves than in control animals. After 8 months PI, however, phagocytosis became equal between the two groups. Random and chemotactic migration and antibody-dependent cell-mediated cytotoxicity (ADCC) did not appear to be affected by BIV infection. Monocytes from BIV infected cattle were able to respond to in vitro treatment with interferon gamma similarly to monocytes from control cattle. Although experimental infection with BIV R29 resulted in minimal effects on monocyte function, this result could have been due either to a low virus burden in vivo or because BIV is intrinsically unable to affect monocyte function. To distinguish between these possibilities, monocytes from control, uninfected cattle were treated with BIV virus in vitro. Treatment of normal monocytes with cell-free virus significantly (P < 0.05) increased phagocytosis and random and chemotactic migration and decreased ADCC, in a dose-dependent manner. It appears, therefore, that the normal function of peripheral blood monocytes in the BIV R29 infected animals may be due to a low virus burden rather than to the inability of BIV to affect monocyte function. The in vitro infection results also raise the possibility that the function of monocyte derived cells at local sites of BIV replication may be altered.

Effect of ewe ovine lentivirus infection on ewe and lamb productivity.

We used a previously described sensitive and specific ovine lentivirus (OLV) recombinant transmembrane (rTM) protein enzyme-linked immunosorbent assay (ELISA) to detect anti-OLV antibodies and define OLV infection in breeding ewes from nine US Meat Animal Research Center (MARC) flocks. We estimated the production impacts of dam rTM ELISA seropositivity on ewe and lamb productivity in the birth-to-weaning interval using production data from 1466 breeding ewes (of which 1242 actually lambed) and their 2452 lambs born in spring 1992 using several multiple linear and logistic regression models. By adjusting for lamb weaning age, gender, type of birth and rearing, birth difficulty, dam age, and flock, the component of ewe or lamb productivity related to ewe OLV infection alone was isolated. The rTM ELISA-negative ewes produced significantly more total weight of weaned lamb per ewe-lambing (3.84 kg) and per ewe ram-exposed (4.95 kg) compared to their OLV-positive flockmates. Negative ewes also weaned 0.11 more lambs per ewe-lambing and 0.09 more lambs per ewe ram-exposed, gave birth to 0.13 more lambs per ewe ram-exposed, and were more likely to lamb after breeding (odds ratio (OR) = 1.9) compared to equivalent OLV-positive ewes. Lambs reared by OLV-negative ewes weighed 0.15 kg more at birth, gained 8 g more per day through weaning, and weighed 0.59 kg more at 56-day weaning. Preweaning mortality was lower (OR = 0.8) among lambs born to OLV-negative compared to OLV-positive ewes, although this difference was not significant. Our results suggest that subclinical OLV infection has important detrimental effects on sheep production which occur in cumulative fashion from breeding through weaning and that OLV control efforts may be financially justified in some sheep flocks.

Species differences in the reaction of cattle to Jembrana disease virus infection.

Jembrana disease virus (JDV), a recently identified bovine lentivirus, causes an acute and severe disease in Bali cattle (Bos javanicus). Clinical Jembrana disease has not been reported in other types of cattle and this has led to the belief that the disease is unique to Bali cattle. This study showed, however, that other types were also susceptible. Infection of Friesian (Bos taurus) and crossbred Bali (Bos javanicus x Bos indicus) cattle induced clinical changes and lesions consistent with those detected in Bali cattle, although they were milder and would consequently have been difficult to detect under field conditions. The inoculated crossbred cattle were viraemic for 3 months and developed an antibody response to the virus that persisted for at least 46 weeks after infection.

Effects on lung compliance, lung volume, and single-breath transfer factor for carbon monoxide in sheep with lentivirus-induced lymphoid interstitial pneumonia.

Static lung compliance, static lung volumes, and transfer factor for carbon monoxide were measured in 12 anesthetized adult Texel ewes seropositive for maedi-visna virus (MVV) and in 11 breed-, sex-, and age-matched seronegative controls. Median static lung compliance in MVV-infected sheep (1.24 L.kPa-1; range, 0.27 to 2.20 L.kPa-1) was not significantly different from that in controls (1.58 L.kPa-1; range, 0.82 to 2.08 L.kPa-1). Median body weight of MVV-infected sheep (56 kg; range, 40 to 75 kg) was significantly (P < 0.05) less than that of controls (65 kg; range, 53 to 87 kg). Median effective alveolar lung volume in MVV-infected sheep (3.36 L; range, 1.44 to 4.52 L) was significantly (P < 0.01) less than that in controls (4.12 L; range, 3.75 to 4.90 L). Median effective end expiratory lung volume in MVV-infected sheep (1.20 L; range, 0.56 to 1.99 L) was significantly (P < 0.001) less than that of controls (1.98 L; range: 1.76 to 2.78 L). Median lung volumes expressed per unit of body weight did not differ significantly between the groups. Median single-breath transfer factor for carbon monoxide in MVV-infected sheep (7.89 mmol.min-1.kPa-1; range, 3.45 to 12.74 mmol.min-1.kPa-1) was significantly (P < 0.001) less than that in controls (14.10 mmol.min-1.kPa-1; range, 10.02 to 18.30 mmol.min-1.kPa-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Immunomodulative effects of bovine immunodeficiency-like virus (BIV)-infection and mixed infection of BIV and bovine leukemia virus on sheep.

Experimental bovine immunodeficiency-like virus (BIV)-infection and mixed infection of BIV and bovine leukemia virus (BLV) were performed on sheep. BIV proviral DNA and anti-BIV antibodies were persistently detected in all BIV-inoculated sheep. A slight increase in lymphocyte counts was observed in BIV-infected sheep, but the percentages of CD4+ and CD8+ cells in sheep peripheral blood mononuclear cells (PBMCs) were not significantly changed. A transient decrease in lymphocyte blastogenic response to concanavalin. A was observed in two of three BIV-infected sheep at 3-6 months after inoculation. From 6 months after BLV-inoculation to sheep which were previously infected with BIV, the numbers of lymphocytes expressing a tumor-associated antigen (TAA) of bovine leukosis were increased compared to those of a sheep inoculated with BLV alone. The BLV titers in PBMCs and the antibody titers against BLV from sheep infected with both BIV and BLV were higher than those of a sheep inoculated with BLV alone.