Teratogenic bluetongue and related orbivirus infections in pregnant ruminant livestock: timing and pathogen genetics are critical.

Congenital infections of domestic animals with viruses in several families, including Bunyaviridae, Flaviridae, Parvoviridae, and Reoviridae, are the cause of naturally occurring teratogenic central nervous system and/or musculoskeletal defects (arthrogryposis) in domestic animals. Congenital infections of ruminant livestock with bluetongue virus (BTV) and some related members of the genus Orbivirus (family Reoviridae) have clearly shown the critical role of gestational age at infection in determining outcome. Specifically, fetuses infected prior to mid-gestation that survive congenital BTV infection are born with cavitating central nervous system defects that range from severe hydranencephaly to cerebral cysts (porencephaly). Generally, the younger the fetus (in terms of gestational age) at infection, the more severe the teratogenic lesion at birth. Age-dependent virus infection and destruction of neuronal and/or glial cell precursors that populate the developing central nervous system are responsible for these naturally occurring virus-induced congenital defects of animals, thus lesions are most severe when progenitor cells are infected prior to their normal migration during embryogenesis. Whereas congenital infection is characteristic of certain BTV strains, notably live-attenuated (modified-live) vaccine viruses that have been passaged in embryonating eggs, transplacental transmission is not characteristic of many field strains of the virus and much remains to be determined regarding the genetic determinants of transplacental transmission of individual virus strains.

Potential role of proinflammatory cytokines in the pathogenetic mechanisms of vascular lesions in goats naturally infected with bluetongue virus serotype 1.

In vitro studies have demonstrated that bluetongue virus (BTV)-induced vasoactive mediators could contribute to the endothelial cells dysfunction and increased vascular permeability responsible of lesions characteristic of bluetongue (BT) like oedema, haemorrhages and ischaemic necrosis in different tissues. However, few in vivo studies have been carried out to clarify the causes of these lesions. The aim of this study was to elucidate in vivo the pathogenetic mechanisms involved in the appearance of vascular lesions in different organs during BT. For this purpose, tissue samples from goats naturally infected with bluetongue virus serotype 1 (BTV-1) were taken for histopathological and immunohistochemical studies to determine the potential role of proinflammatory cytokines (tumour necrosis factor alpha, TNFα and interleukin one alpha, IL-1α) in the increased vascular permeability and their relationship with the presence of virus. Gross and histopathological examination revealed the presence of vascular damage leading to generalized oedema and haemorrhages. Immunohistochemical studies displayed that endothelial injury may have been due to the direct pathogenic effect of BTV infection on endothelial cells or may be a response to inflammatory mediators released by virus-infected endothelial cells and, possibly, other cell types such as monocytes/macrophages. These preliminary results of what appears to be the first in vivo study of tissue damage in small BT-infected ruminants suggest a direct link between the appearance of vascular changes and the presence of BTV-induced vasoactive cytokines.

Aspectos epidemiológicos y entomólogicos de la enfermedad de lengua azul en ganado bovino / Epidemiologic and entomologic aspects of bluetongue in cattle in the Isthmus of Tehuantepec, Oaxaca, Mexico

Se realizó un estudio prospectivo de la enfermedad de lengua azul en 2 hatos de ganado bovino en la región del Istmo de Tehuantepec. El estudio incluyó la detección menstrual de anticuerpos grupo-específicos contra el virus de lengua azul (VLA) y la captura de moscas culicoides. En enero de 1988, el total de ganado bovino en los 2 hatos (600) fue clasificado seropositivo al VLA, utilizando un método ELISA. Con base en este resultado, 40 bovinos adultos y 35 becerros nacidos entre octubre de 1987 y enero de 1988 fueron evaluados mensualmente (enero a diciembre de 1988) para detectar la producción de anticuerpos grupo-específicos VLA. Se detectó un patrón positivo de seroconversión contra el VLA en becerros, durante la temporada de lluvia en los meses del verano (junio-septiembre). Sin embargo, en algunos becerros se determinó serológicamente actividad de VLA en la temporada seca, durante marzo y abril. Debido a la ausencia de anticuerpos maternos, la mayoría de los becerros fueron susceptibles de infección con el VLA a los 6 meses de edad. La evidencia serológica de la actividad del VLA en becerros se relacionó con la abundancia de moscas Culicoides insignis capturadas durante el estudio

Experimentally induced bluetongue virus infection in white-tailed deer: coagulation, clinical pathologic, and gross pathologic changes.

Ten yearling white-tailed deer (Odocoileus virginianus) were inoculated with bluetongue virus serotype 17. Two yearling white-tailed deer were inoculated with sonicated heparinized noninfected blood and served as controls. Clinical signs of bluetongue virus infection included increased rectal temperature, erythema, facial edema, coronitis, and stomatitis. By postinoculation day (PID) 8, excessive bleeding and hematoma formation at venipuncture sites, dehydration, and diarrhea developed. At necropsy, the most consistent findings were oral lesions and widespread hemorrhage, which ranged from petechia to massive hematoma formation. Bluetongue virus caused progressive prolongation of activated partial thromboplastin time and prothrombin time, and progressive reduction of Factors VIII and XII plasma activities beginning on PID 6. A progressive decrease in platelet numbers also developed on PID 6. Changes in platelet size were not detected. Mean thrombin time was shortened, but prolongation developed in 1 deer. Mean fibrinogen concentration and Factor V plasma activity initially increased and then decreased, but remained above preinoculation values. Factor V activity was low in a few deer. Results of screening tests for inhibitors of the intrinsic coagulation system were positive in 2 deer. High concentrations of fibrin(ogen) degradation products were first detected between PID 3 and 6. Hematologic changes included leukopenia, lymphopenia, neutrophilia, and low total plasma protein concentration. Differences in PCV, hemoglobin concentration, or RBC counts were not detected between infected and control deer. Serum total bilirubin concentration increased by PID 6, primarily because of increased unconjugated bilirubin concentration. Mild to severe increases in serum aspartate transaminase activity were accompanied by more marked increases in creatine kinase activity. Indirect Coombs test results were negative in all deer.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimentally induced bluetongue virus infection in white-tailed deer: ultrastructural findings.

White-tailed deer (Odocoileus virginianus) were inoculated with bluetongue virus serotype 17 and sequentially euthanatized during infection. Ultrastructural changes in the microvasculature of tongue, buccal mucosa, heart, and pulmonary artery, platelets, and bone marrow were evaluated. Bluetongue virus was found in endothelial cells of the microvasculature by postinoculation day 4. Viral replication was associated with the development of viral matrices, viral-associated macrotubules, and aggregates of mature viral particles in the cytoplasm of infected cells. Viral infection of pericytes and vascular smooth muscle cells developed subsequent to endothelial cell infection. Viral infection was associated with striking changes in the endothelial lining of the microvasculature by postinoculation day 4. Endothelial cell degeneration and necrosis, which resulted in denudation of the endothelial lining, and endothelial cell hypertrophy frequently were observed. Thrombosis, hemorrhage, and vessel rupture developed subsequent to endothelial damage. Bluetongue virus neither infected nor directly damaged platelets or bone marrow cells. It was concluded that viral-induced endothelial damage is the primary triggering mechanism for disseminated intravascular coagulation in bluetongue virus infection. Vascular damage coupled with the development of disseminated intravascular coagulation is responsible for the hemorrhagic diathesis, which is characteristic of bluetongue virus infection in white-tailed deer.