Jaagsiekte Sheep Retrovirus Infection Research Articles

A survey of jaagsiekte sheep retrovirus (JSRV) infection in sheep in the three northeastern provinces of China

Ovine pulmonary adenomatosis (OPA) is caused by jaagsiekte sheep retrovirus (JSRV) and is a chronic, progressive, and infectious neoplastic lung disease in sheep, which causes significant economic losses to the sheep industry. Neither a vaccine nor serological diagnostic methods to detect OPA are available. We performed a JSRV infection survey in sheep using blood samples (n = 1,372) collected in the three northeastern provinces of China (i.e., Inner Mongolia, Heilongjiang, and Jilin) to determine JSRV infection status in sheep herds using a real-time PCR assay targeting the gag gene of JSRV. The ovine endogenous retrovirus sequence was successfully amplified in all sheep samples tested (296 from the Inner Mongolia Autonomous Region, 255 from Jilin province, and 821 from Heilongjiang province). Subsequently, we attempted to distinguish exogenous JSRV (exJSRV) and endogenous JSRV (enJSRV) infections in these JSRV-positive samples using a combination assay that identifies a ScaI restriction site in an amplified 229-bp fragment of the gag gene of JSRV and a "LHMKYXXM" motif in the cytoplasmic tail region of the JSRV envelope protein. The ScaI restriction site is present in all known oncogenic JSRVs but absent in ovine endogenous retroviruses, while the "LHMKYXXM" motif is in all known exJSRVs but not in enJSRVs. Interestingly, one JSRV strain (HH13) from Heilongjiang province contained the "LHMKYXXM" motif but not the ScaI enzyme site. Phylogenetic analysis showed that strain HH13 was closely related to strain enJSRV-21 reported in the USA, indicating that HH13 could be an exogenous virus. Our results provide valuable information for further research on the genetic evolution and pathogenesis of JSRV.

An approach to diagnosis of Jaagsiekte sheep retrovirus infection in sheep based on assessment of agreement between macroscopic examination, histopathologic examination and reverse-transcriptase polymerase chain reaction

Abstract Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). JSRV infection is usually detected post-mortem by macroscopic and histological examination of lungs for lesions of OPA. Subsequently, the presence of JSRV may be confirmed using polymerase chain reaction (PCR) on tumour tissue. Our goal was to determine the most effective way of combining macroscopic and histological examination with reverse transcriptase PCR (RT-PCR) to detect JSRV infection post-mortem. Lungs of slaughtered sheep (n = 369) with macroscopic lesions were examined macroscopically and histologically to identify lesions consistent with OPA, and subsequently subjected to RT-PCR for JSRV. Positive (Ppos) and negative (Pneg) agreement and Cohen’s Kappa were calculated between RT-PCR and: 1) macroscopic examination; 2) histological examination; 3) macroscopic and histological examinations combined in series, and 4) in parallel. The highest Ppos was between macroscopic and histological examination in parallel and RT-PCR (0.38). Conversely, Pneg for all combinations of RT-PCR and macroscopic and histological examinations was high (0.95-0.96). All Kappa values were low (0.1-0.33). This indicates that macroscopic and histological examination combined in parallel is the most effective way to identify animals that should be tested using RT-PCR for JSRV. If a positive result is obtained on macroscopic examination and/or histological examination, RT-PCR for JSRV should be carried out. The high Pneg indicates that if a negative result is obtained on macroscopic and histological examination, RT-PCR testing is not merited, as the result is likely to be negative. This provides an evidence-base for the diagnosis of JSRV infection.

Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

Patho-Epidemiological study of jaagsiekte sheep retrovirus infection in the sheep and goats population, India

ABSTRACT An epidemiological study was conducted along with pathological, immunohistochemistry (IHC) of capsid antigen and molecular detection of jaagsiekte sheep retrovirus (JSRV) causing ovine pulmonary adenocarcinoma (OPA) in sheep and goats population from three states of India viz. Delhi, Gannavaram (Andhra Pradesh), and Bareilly (Uttar Pradesh). A total of 1350 lungs samples were screened and out of which 31 (2.29%) animals were found to be positive [sheep (3.49%) and goats (0.00%)] for JSRV. The prevalence of infection was recorded Gannavarum (20.00%) followed by Delhi (2.10%) and no any positive cases found in Bareilly area. Age wise higher prevalence was recorded >3 year age groups followed by 1–3 years and 1 < year, respectively. Significantly, higher infection was observed in female sheep compared to male sex of sheep. Seasonally, the prevalence of JSRV infection was higher in monsoon (6.00%) followed winter season (3.34%) and summer season. The observations of the present study would provide basis for further an effective explorative surveillance and epidemiological studies to know real impact of JSRV infection circulating in sheep and goats population of India.

First confirmation by PCR of Jaagsiekte sheep retrovirus in Ireland and prevalence of ovine pulmonary adenocarcinoma in adult sheep at slaughter

BackgroundOvine pulmonary adenocarcinoma (OPA), caused by Jaagsiekte sheep retrovirus (JSRV), is characterised by the development of invariably fatal lung tumours primarily in adult sheep. High infection rates and disease prevalence can develop during initial infection of flocks, leading to on-farm economic losses and animal welfare issues in sheep with advanced disease. The disease has been reported in Ireland and is notifiable, but the presence of JSRV has never been confirmed using molecular methods in this country. Additionally, due to the difficulties in ante-mortem diagnosis (especially of latently-infected animals, or those in the very early stages of disease), accurate information regarding national prevalence and distribution is unavailable. This study aimed to confirm the presence of JSRV in Ireland and to obtain estimates regarding prevalence and distribution by means of an abattoir survey utilising gross examination, histopathology, JSRV-specific reverse transcriptase polymerase chain reaction (RT-PCR) and SU protein specific immunohistochemistry (IHC) to examine the lungs of adult sheep.ResultsLungs from 1911 adult sheep were examined macroscopically in the abattoir and 369 were removed for further testing due to the presence of gross lesions of any kind. All 369 were subject to histopathology and RT-PCR, and 46 to IHC. Thirty-one lungs (31/1911, 1.6%) were positive for JSRV by RT-PCR and/or IHC but only ten cases of OPA were confirmed (10/1911, 0.5%) Four lung tumours not associated with JSRV were also identified. JSRV-positive sheep tended to cluster within the same flocks, and JSRV-positive sheep were identified in the counties of Donegal, Kerry, Kilkenny, Offaly, Tipperary, Waterford and Wicklow.ConclusionsThe presence of JSRV has been confirmed in the Republic of Ireland for the first time using molecular methods (PCR) and IHC. In addition, an estimate of OPA prevalence in sheep at slaughter and information regarding distribution of JSRV infection has been obtained. The prevalence estimate appears similar to that of the United Kingdom (UK). Results also indicate that the virus has a diverse geographical distribution throughout Ireland. These data highlights the need for further research to establish national control and monitoring strategies.

Changes in blood parameters induced by experimental jaagsiekte sheep retrovirus infection

Abstract The aim of the study was to assess the changes of blood parameters in 12 three-week-old Polish Merino sheep subjected to experimental jaagsiekte sheep retrovirus (JSRV) infection. Material and Methods: Haematological (WBC with leukocyte subpopulations: GRA, LYM, MID, and RBC, MCV, MCH, MCHC, HGB, HCT, PLT, and MPV) and biochemical blood parameters (acid/base balance, cation/anion content, and gasometry) were determined in blood samples collected one month after JSRV infection, then at four-week intervals for five consecutive months. Results: A decrease in RBC, HCT, MCV, PLT, MPV, and LYM values in comparison with controls was found in the last month of observation. On the other hand, at the same time, an increase in HGB, MCH, MCHC, WBC, MID, and GRA indices was observed. Moreover, at the end of experiment blood gasometric indices such as pCO2, HCO3, and tCO2, and Na and K ion concentrations were higher in the affected lambs than in the healthy animals. The pH values of the challenged animals exhibited less alkaline character than in the case of controls, which was associated with a decrease in O2% saturation. However, the majority of differences between JSRV inoculated and control groups was not statistically significant. Conclusion: The observed changes in the examined blood parameters can be considered as prodromal symptoms in the preclinical phase of adenocarcinoma development associated with JSRV infection.

Jaagsiekte Sheep Retrovirus Can Reach Peyer's Patches and Mesenteric Lymph Nodes of Lambs Nursed by Infected Mothers.

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). It is generally accepted that transmission by the respiratory route occurs under natural conditions. However recent studies strongly indicate that JSRV can also be transmitted to lambs perinatally via colostrum and milk (C/M). The aim of this work was to confirm that C/M can transmit JSRV infection to lambs under natural conditions and investigate the initial events associated with this transmission route. We have analyzed the presence of JSRV in C/M samples from 22 naturally infected, asymptomatic ewes throughout a lactation period, and in various tissues collected from a group of 36 of their lambs that were fed naturally. The lambs were euthanized at 12, 24, 48, and 72 hours and at 5 and 10 days after birth. We detected JSRV-provirus by PCR in the somatic C/M cells from 10/22 ewes (45.45%). The virus was also detected in 9/36 lambs (25%). JSRV-infected cells, with lymphoreticular-like morphology, were observed by immunohistochemistry (IHC) and in situ hybridization (ISH) in Peyer's patches (PP) from the small intestine of the youngest lambs and in mesenteric lymph nodes (MLN) from lambs older than 72 hours. The virus was also detected by PCR in white blood cells (WBC) in 2/36 lambs (5.5%). These results confirm colostral transmission of JSRV to lambs under natural conditions. Infected lymphoreticular cells contained in C/M appear to be involved. These cells can cross the intestinal barrier of newborn lambs, reach the MLN and enter into circulation.

Assessment of transthoracic ultrasound diagnosis of ovine pulmonary adenocarcinoma in adult sheep

Ovine pulmonary adenocarcinoma (OPA), caused by Jaagsiekte sheep retrovirus (JSRV), is a disease of increasing concern in the sheep industry. There is no commercial antemortem test for OPA; therefore, an...

Application of next generation sequencing in mammalian embryogenomics: Lessons learned from endogenous betaretroviruses of sheep

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. The sheep genome contains 27 JSRV-related endogenous betaretroviruses (enJSRVs) related to the pathogenic Jaagsiekte sheep retrovirus (JSRV) that have been integrating in the host genome for the last 5–7 million years. The exogenous JSRV is a causative agent of a transmissible lung cancer in sheep, and enJSRVs are able to protect the host against JSRV infection. In sheep, the enJSRVs are most abundantly expressed in the uterine epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm. Sixteen of the 27 enJSRV loci contain an envelope (env) gene with an intact open reading frame, and in utero loss-of-function experiments found the enJSRVs Env to be essential for trophoblast outgrowth and conceptus elongation. Collectively, available evidence supports the ideas that genes captured from ancestral retroviruses were pivotal in the acquisition of new, important functions in mammalian evolution and were positively selected for biological roles in genome plasticity, protection of the host against infection of related pathogenic and exogenous retroviruses, and a convergent physiological role in placental morphogenesis and thus mammalian reproduction. The discovery of ERVs in mammals was initially based on molecular cloning discovery techniques and will be boosted forward by next generation sequencing technologies and in silico discovery techniques.

Interplay Between JSRV, an Oncogenic Retrovirus, and the Pulmonary Epithelium

Jaagsiekte sheep retrovirus (JSRV) is a retrovirus which infects small ruminants and is responsible for a natural lung cancer. This virus bears an oncogenic envelope inducing epithelial cell transformation from the deep lung. The cells, main target of the infection and constitutive of the tumors, are alveolar type II cells in the alveoli and Clara cells in the bronchioli. The immune response to JSRV infection is poorly understood. The specific humoral response is limited and the cell-mediated response is marked by CD4+ lymphocytopenia, neutrophilia, and macrophage invasion of the tumor. The mechanisms of viral immune evasion could be explained by the direct and indirect immunosuppressive effects of the virus, and by the immune tolerance of the infected hosts due to the presence in the sheep genome of endogenous viral forms (enJSRV). Keywords: Adenocarcinoma, alveolar type II cells, immune response, JSRV, lung, Jaagsiekte sheep retrovirus, lung cancer, infection, enJSRV, Ovine Pulmonary Adenocarcinoma

Endogenous Retroviruses of Sheep: A Model System for Understanding Physiological Adaptation to an Evolving Ruminant Genome

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

Jaagsiekte sheep retrovirus infects multiple cell types in the ovine lung.

Ovine pulmonary adenocarcinoma (OPA) is a transmissible lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The details of early events in the pathogenesis of OPA are not fully understood. For example, the identity of the JSRV target cell in the lung has not yet been determined. Mature OPA tumors express surfactant protein-C (SP-C) or Clara cell-specific protein (CCSP), which are specific markers of type II pneumocytes or Clara cells, respectively. However, it is unclear whether these are the cell types initially infected and transformed by JSRV or whether the virus targets stem cells in the lung that subsequently acquire a differentiated phenotype during tumor growth. To examine this question, JSRV-infected lung tissue from experimentally infected lambs was studied at early time points after infection. Single JSRV-infected cells were detectable 10 days postinfection in bronchiolar and alveolar regions. These infected cells were labeled with anti-SP-C or anti-CCSP antibodies, indicating that differentiated epithelial cells are early targets for JSRV infection in the ovine lung. In addition, undifferentiated cells that expressed neither SP-C nor CCSP were also found to express the JSRV Env protein. These results enhance the understanding of OPA pathogenesis and may have comparative relevance to human lung cancer, for which samples representing early stages of tumor growth are difficult to obtain.

Surveillance of Jaagsiekte Sheep Retrovirus in Sheep in Hokkaido, the Northern Island of Japan

Surveillance of jaagsiekte sheep retrovirus (JSRV) infection was performed by polymerase chain reaction (PCR) of blood DNA samples collected from 40 sheep and goats in 10 different flocks in Hokkaido, the northern island of Japan. No exogenous (oncogenic) JSRV sequence was detected by PCR in these samples, while the ovine endogenous retrovirus sequence was successfully amplified in all samples. Our paper is the first demonstration of JSRV surveillance in Japan and shows no evidence of oncogenic JSRV infection in sheep and goats in Hokkaido.

Jaagsiekte Sheep Retrovirus Biology and Oncogenesis

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of a lung cancer in sheep known as ovine pulmonary adenocarcinoma (OPA). The disease has been identified around the world in several breeds of sheep and goats, and JSRV infection typically has a serious impact on affected flocks. In addition, studies on OPA are an excellent model for human lung carcinogenesis. A unique feature of JSRV is that its envelope (Env) protein functions as an oncogene. The JSRV Env-induced transformation or oncogenesis has been studied in a variety of cell systems and in animal models. Moreover, JSRV studies have provided insights into retroviral genomic RNA export/expression mechanisms. JSRV encodes a trans-acting factor (Rej) within the env gene necessary for the synthesis of Gag protein from unspliced viral RNA. This review summarizes research pertaining to JSRV-induced pathogenesis, Env transformation, and other aspects of JSRV biology.

Endogenous retroviruses of sheep: a model system for understanding physiological adaptation to an evolving ruminant genome

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Sheep betaretroviruses offer a unique model system to study the complex interaction between retroviruses and their host. The sheep genome contains 27 endogenous betaretroviruses (enJSRVs) related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. The enJSRVs can protect their host against JSRV infection by blocking early and late steps of the JSRV replication cycle. In the female reproductive tract, enJSRVs are specifically expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophectoderm growth and development. Collectively, available evidence in sheep and other mammals indicate that ERVs coevolved with their hosts for millions of years and were positively selected for biological roles in genome plasticity and evolution, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental development.

Endogenous Retroviruses: From Infectious Elements to Essential Genes.

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and are remnants of ancient exogenous retroviral infections of the host germline transmitted vertically from generation to generation. Syncytins are envelope (env) genes of retroviral origin that have been co-opted by the host to mediate placental development. Two syncytin genes have been identified in primates (HERV-W (ERVWE1) termed syncytin-1 and HERV-FRD termed syncytin-2), as well as distinct, nonorthologous genes in rodents (syncytin-A and -B) and rabbits (syncytin-Ory1). The syncytins can induce cell-cell fusion, and placental development in those mammals requires the fusion of trophoblast cells into a highly specialized, multinucleated syncytiotrophoblast layer, which is essential for absorption of nutrients from the mother. All of the syncytins are expressed in the syncytiotrophoblasts, and null mutation of the syncytin-A gene in mice results in disruption of the syncytiotrophoblast-containing labyrinth placenta. The null placentae exhibit decreased vascularization and poor transport, resulting in fetal growth retardation and ultimately embryo loss between 11.5 and 13.5 days of gestation. In both humans and mice, one of the two syncytins (human syncytin-2 and mouse syncytin-B) is also immunosuppressive, suggesting they may be also involved in immunotolerance of the semiallogeneic fetus. The sheep genome contains 27 JSRV-related endogenous betaretroviruses (enJSRVs) related to the pathogenic Jaagsiekte sheep retrovirus (JSRV) that have been integrating in the host genome for the last 5-7 million years. The exogenous JSRV is a causative agent of a transmissible lung cancer in sheep, and enJSRVs are able to protect their host against JSRV infection by blocking different steps of the viral replication cycle via receptor interference and late replication steps. Indeed, endogenization and positive selection of ERVs acting as restriction factors is a mechanism used by the host to fight exogenous retroviral infections. In sheep, the enJSRVs are most abundantly expressed in the uterine luminal and glandular epithelia as well as in the conceptus (embryo and associated extraembryonic membranes) trophectoderm. Sixteen of the 27 enJSRV loci contain an env gene with an intact open reading frame, and in utero loss-of-function experiments found the enJSRVs envelope (env) to be essential for conceptus elongation and trophoblast growth and differentiation. Collectively, available evidence supports the ideas that genes captured from ancestral retroviruses have been pivotal in the acquisition of new, important functions in mammalian evolution and were positively selected for biological roles in genome plasticity, protection of the host against infection of related pathogenic and exogenous retroviruses, and placental morphogenesis. This work supported by NIH Grant HD052745 and by a Strategic Research Developmental Grant by the Scottish Funding Council. (platform)

Friendly viruses: the special relationship between endogenous retroviruses and their host.

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and have coevolved with their hosts for millions of years. Some ERVs play a critical role in placental development, contribute to genome plasticity, and protect the host against infection of related pathogenic and exogenous retroviruses, thus some ERVs have been positively selected and maintained in the host genome. The sheep genome contains 27 endogenous retroviruses (enJSRVs) related to the pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. enJSRVs are able to protect their host against JSRV infection by blocking different steps of the viral replication cycle. In addition, enJSRVs are absolutely required for sheep placental development. Thus, enJSRVs-JSRV provides a unique and interesting model to study the symbiotic relationship and interplay between host ERVs and evolution. This review will provide some examples of the biological functions of ERVs. In particular, the role of ERVs in reproductive biology and in protecting the host against pathogenic retrovirus infections will be emphasized using enJSRVs/JSRV and the sheep as a model.

Colostrum and milk can transmit jaagsiekte retrovirus to lambs

Ovine pulmonary adenocarcinoma (OPA) is a contagious disease caused by jaagsiekte sheep retrovirus (JSRV). In the three studies performed, we have obtained data of the importance of colostrum/milk (C/M) in the transmission of JSRV. In the first study, a group of sheep from a flock with a long history of OPA, samples from colostrum and peripheral blood leucocytes (PBLs) were collected. Two specific PCRs (U3-LTR and env of the JSRV) were carried out. Using U3PCR 8/34 sheep were positive in colostrum whereas with envPCR 7/34 were positive. From these animals only one was positive with U3PCR in the PBLs. Evidence of the transmission of JSRV infection by C/M was obtained in two more separate studies. In the second study, PBLs from five lambs from JSRV+ ewes and two from JSRV-ewes were tested by the U3PCR. They were fed C/M by their mothers during 3 months and slaughtered 7 months after birth. Three out of five lambs from the JSRV+ sheep become PBL positive at 3–4 months old and the other two were also positive at 4–6 months of age. One lamb of the JSRV-sheep became also PBL positive at an age of 3 months. In the third study, a group of lambs from JSRV negative mothers were fed with C/M from JSRV+ sheep and housed in separate unit. For comparison, another group of the same origin and maintained in another different unit, were fed with C/M containing a JSRV virus preparation. All lambs were blood sampled monthly and JSRV infection was detected as early as 15 days and several times onwards in both groups. Control groups fed with C/M from JSRV free flock and JSRV blood test negative sheep were always negative. Together these results indicate that suckling is an important natural transmission route for JSRV.

Jaagsiekte sheep retrovirus utilizes a pH-dependent endocytosis pathway for entry.

Using Moloney murine leukemia virus pseudovirions bearing the envelope protein of Jaagsiekte sheep retrovirus (JSRV), we report here that entry was weakly inhibited by lysosomotropic agents but was profoundly blocked by bafilomycin A1 (BafA1). Kinetics studies revealed that JSRV entry is a slow process and was substantially blocked by a dominant-negative mutant of dynamin. Interestingly, a low-pH pulse overcame the BafA1 block to JSRV infection, although this occurred only if virus-bound cells were preincubated at 37 degrees C, consistent with a very early entry event such as endocytosis being required before the low-pH-dependent step occurs. Moreover, JSRV pseudovirions were resistant to low-pH inactivation. Altogether, this study reveals that JSRV utilizes a pH-dependent, dynamin-associated endocytosis pathway for entry that differs from the classical pH-dependent entry pathway of vesicular stomatitis virus.