Immunohistochemical Detection of the p27 Capsid Protein of Caprine Arthritis–Encephalitis Virus (CAEV) in Bone-marrow Cells of Seropositive Goats

Grossi, Paolo; Giudice, Chiara; Bertoletti, I.; Cioccarelli, G.; Brocchi, Emiliana; Cammarata, G.; Gelmetti, Daniela

doi:10.1016/j.jcpa.2005.01.009

Cited by 14 publications

(5 citation statements)

References 10 publications

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“…It has been suggested that these cells may act as a reservoir of infected stem cells. Viral antigen is also expressed in bone marrow stromal cells [11] and it may be these that infect monocyte precursors. However, the frequency and importance of bone marrow infection has been questioned using PCR based methods [12].…”

Section: Cell Tropismmentioning

confidence: 99%

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

Blacklaws

Harkiss²

2010

CHR

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Small ruminant lentiviruses (SRLV) and human immunodeficiency viruses (HIV) are related retroviruses that cause multisystem disease usually over a long period of time. The viruses show similarities and differences in biological and pathogenic features. The basic retroviral genomic organization is complicated by the presence of a variable number of accessory genes in both viruses, though the structure is more complex in HIV. Both are mucosal pathogens, and infect cells of the monocyte-macrophage lineage. The main difference in cell tropism is that, unlike HIV, SRLV do not infect lymphocytes. A major feature of both pathogens is restricted replication and virus latency, which are partly responsible for the establishment of chronic infection usually lasting for life. The pathologies observed are similar in the early stages of both infections, and possibly following highly active anti-retroviral therapy (HAART). While the pathogenesis of HIV-induced disease during symptomatic stages is mainly due to secondary infections and neoplastic conditions, the early and post-HAART stages are associated with chronic inflammatory changes that resemble those found in SRLV diseases which are thought to be mediated by anti-virus immune responses.

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Section: Cell Tropismmentioning

confidence: 99%

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

Blacklaws

Harkiss²

2010

CHR

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“…Circulating monocytes latently infected by the dUTPase-deficient virus may be the result of an infection occurring in the myeloid precursors, providing a cellular environment typical of actively dividing cells, known to be necessary for compensating the lack of viral dUTPase (20). Therefore, it is important to establish the role of bone marrow as a virus reservoir in genotype E infection, which is still controversial in dUTPase-positive strains (6,14). In addition, in all previous studies in which dUTPase, vpr-like, and U3 70-bp repeat sequences were independently deleted from the CAEV genome, a reduction in viral load and/or disease progression was recorded, thus providing indirect evidence that genotype E exhibits a low-pathogenicity potential in vivo (9,11,20).…”

mentioning

confidence: 99%

Genome Analysis of Small-Ruminant Lentivirus Genotype E: a Caprine Lentivirus with Natural Deletions of the dUTPase Subunit, vpr -Like Accessory Gene, and 70-Base-Pair Repeat of the U3 Region

Reina

Grego

Bertolotti

et al. 2009

J Virol

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The nucleotide sequence of the highly divergent small-ruminant lentivirus genotype E has been determined. The full genome consists of 8,418 nucleotides and lacks two large portions corresponding nearly to the entire dUTPase subunit of the pol and vpr-like accessory genes. Moreover, the 70-bp repeat of the U3 region of the long terminal repeat was observed to be deleted. Interestingly, this lentivirus genotype is able to persist in a local breed population, and retrospective analysis revealed its presence in milk samples collected in 1999. gag sequences obtained from a flock coinfected with the B1 and E genotypes revealed that the evolutionary rates of the two viruses were quite similar. Since a reduced viral load and/or disease progression was observed for viruses with artificially deleted dUTPase and vpr-like genes, it is proposed that this viral cluster be designated a low-pathogenicity caprine lentivirus.The small-ruminant lentiviruses (SRLVs) are a genetically and antigenically heterogeneous group of viruses infecting sheep and goats, leading to persistent infection and chronic debilitating diseases. The majority of SRLV isolates can be classified into two main phylogenetic clusters: genotype A, involving maedi-visna virus-like strains, and genotype B, including caprine arthritis-encephalitis virus (CAEV)-like isolates, originally isolated from sheep and goats, respectively. Additional genotypes include Norwegian (genotype C) (4) and Swiss and Spanish (genotype D) (15, 18) isolates and the recently described Italian caprine isolates (genotype E) identified in flocks in which the local Roccaverano goat breed was prevalent (5). Interestingly, as for other indigenous goat breeds, typical clinical signs of lentiviral infection had never been observed in Italy before the introduction of imported breeds carrying the B1 subtype in the early 1980s.SRLVs possess a complex genome comprising the gag, pol, and env structural genes and the vif, tat, and rev accessory genes. The low-pathogenicity SRLVs characterized so far have shown that deletions or mutations in the long terminal repeat (LTR) may be associated with variations in virulence, likely due to the presence of replication enhancer elements such as AP1, AML, tumor necrosis factor-␣, and gamma interferon response elements (1, 11). Additional information about virulence factors has been produced in in vitro and in vivo studies by using genetic manipulation of infectious molecular clones (7,8,10,19,23). The dUTPase subunit, encoded by the pol gene, has been found to be dispensable for viral replication (12); however, dUTPase-negative strains produce less-severe lesions, restricted to the injection site (20). The tat gene of SRLV has been recently designated vpr-like, based on its primary protein structure and some functional similarities to human immunodeficiency virus type 1 Vpr protein (21). The CAEV tat (hereafter named vpr-like) gene increases the viral load, tissue distribution, and inflammatory lesion severity over that of the vpr deletion counterpart (9).In ...

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“…Several singlelabel immunohistochemical (IHC) analyses have been developed to detect OPPV, MVV, or CAEV proteins. SRLV capsid antigen (CA) has been detected in lung, bronchoalveolar lavage cells, mammary gland, lymph nodes, carpal synovial membrane, heart, liver, lymphoid tissue associated with the third eyelid, bone marrow, and the central nervous system, 4,5,8,10,19,21,37,51 with the mouse monoclonal antibodies (MAbs) 3F 37 generated to OPPV 85/34, 1A7 19 generated to MVV, and VPM70 49 generated to MVV EV1 CA or a rabbit polyclonal antibody 51 raised to a recombinant CAEV T9 CA protein. MVV CA has also been detected in tissue sections of kidney, gastrointestinal tract, and lung 2,46,47 of sheep, with the anti-CAEV-63 CA MAb 5A1.…”

mentioning

confidence: 99%

Ovine Progressive Pneumonia Virus Capsid Antigen as Found in CD163- and CD172a-Positive Alveolar Macrophages of Persistently Infected Sheep

et al. 2009

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In situ detection of ovine progressive pneumonia virus (OPPV) and the phenotypic identification of the cells that harbor OPPV have not been described for the OPPV-affected tissues, which include lung, mammary gland, synovial membranes of the carpal joint, and choroid plexus of the brain. In this study, the authors first developed a single enzyme-based automated immunohistochemical (IHC) analysis for detection of OPPV capsid antigen (CA) on OPPV-affected tissues, using 2 anti-CAEV CA monoclonal antibodies, 5A1 and 10A1, and 2 enzyme-based IHC systems. Out of 10 naturally and persistently OPPVinfected ewes, OPPV CA was detected in intercellular regions of the carpal synovial membrane of 1 ewe, in cells resembling alveolar macrophages and pulmonary interstitial macrophages in lung tissue of 3 ewes, and in mammary alveolar cells of 1 ewe. Furthermore, dual enzyme-based automated IHC analyses revealed that OPPV CA was predominantly detected in CD172a-or CD163-positive alveolar macrophages of the lungs and mammary gland. That anti-inflammatory (CD163) and downregulatory (CD172a) types of alveolar macrophage harbor OPPV CA leads to the possibility that during persistent infection with OPPV, the host alveolar macrophage might serve to limit inflammation while OPPV persists undetected by the host adaptive immune response in the lung and mammary gland.Keywords ovine progressive pneumonia virus, maedi-visna virus, ovine lentivirus, capsid, dual immunohistochemistry, CD163, CD172aThe small ruminant lentiviruses (SRLVs), including ovine progressive pneumonia virus (OPPV), maedi-visna virus (MVV), and caprine arthritis-encephalitis virus (CAEV), are phylogenetically similar and are part of the Retroviridae family, which includes human immunodeficiency virus (HIV). 54Clinical signs of SRLV include dyspnea, firmness of the udder and/or reduced milk production (mastitis), swollen joints and lameness (arthritis), cachexia, and ataxia. Clinical signs can vary in animals; therefore, the reference standard for evaluating the extent of disease caused by SRLVs is postmortem histological assessment of lung, mammary gland, carpal synovial membrane, and choroid plexus. 7,11,13 Definitive diagnosis of SRLV infection cannot be made on the sole basis of histopathology; as such, serological (enzyme-linked immunosorbent assay [ELISA]) and/or molecular (polymerase chain reaction [PCR]) diagnostic tests are used to establish the presence of infection. 15The SRLVs are considered immunopathological diseases, meaning that subsequent immune responses to the virus are thought to contribute more to the pathology of the disease than to the virus alone. 12 The histological progression of SRLV-induced pathology in the tissues is thought to follow a general pattern whereby there is increased lymphoid follicle development and mononuclear and plasma cell infiltration, as followed by edema and necrosis of tissues in severe cases. In MVV-infected sheep, more MHC class II-positive cells and CD8-positive cells are observed in the bronchoalveolar lavage...

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Immunohistochemical Detection of the p27 Capsid Protein of Caprine Arthritis–Encephalitis Virus (CAEV) in Bone-marrow Cells of Seropositive Goats

Cited by 14 publications

References 10 publications

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

Genome Analysis of Small-Ruminant Lentivirus Genotype E: a Caprine Lentivirus with Natural Deletions of the dUTPase Subunit, vpr -Like Accessory Gene, and 70-Base-Pair Repeat of the U3 Region

Ovine Progressive Pneumonia Virus Capsid Antigen as Found in CD163- and CD172a-Positive Alveolar Macrophages of Persistently Infected Sheep

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