M Juganaru

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (4)9.43 Total impact

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    ABSTRACT: Small ruminant lentiviruses (SRLVs) represent a group of viruses infecting sheep and goats worldwide. Despite the high heterogeneity of genotype A strains, which cluster into as many as ten subtypes, genotype B was believed to be less complex and has, so far, been subdivided into only two subtypes. Here, we describe two novel full-length proviral sequences isolated from Sarda sheep in two Italian regions. Genome sequence as well as the main linear epitopes clearly placed this cluster into genotype B. However, owing to long-standing segregation of this sheep breed, the genetic distances that are clearly >15 % with respect to B1 and B2 subtypes suggest the designation of a novel subtype, B3. Moreover the close relationship with a gag sequence obtained from a Turkish sheep adds new evidence to historical data that suggest an anthropochorous dissemination of hosts (small ruminants) and their pathogens (SRLV) during the colonization of the Mediterranean from the Middle East.
    Journal of General Virology 05/2011; 92(Pt 8):1923-9. · 3.13 Impact Factor
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    ABSTRACT: Small ruminant lentivirus genotype E lacks the dUTPase subunit and vpr-like gene. Two strains (Roccaverano and Seui) with identical genetic organization have been described, with the env HV1-HV2 domains being the most divergent. Although dUTPase and vpr-like deletions have been involved in the RT fidelity in non dividing cells, both strains were able to replicate efficiently in blood derived macrophages (BDM), while virus production of E1 subtype was reduced or abrogated in replicating fibroblastic-like cells. The transcriptional activity of genotype E was similar in these two cellular populations. When viral pseudotypes were generated with the env of both viruses, Roccaverano pseudotype displayed a paranuclear localization on BDM, suggesting a different mechanism of entry. Polymorphic GAS and TAS sites in the U3 region, further suggest that a population different from classically activated macrophages can be infected by these viruses, opening new insights into lentiviruses with low or null pathogenic potential.
    Virology 02/2011; 410(1):88-95. · 3.35 Impact Factor
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    ABSTRACT: Genotype E of small ruminant lentivirus has been recently described in goats from different breeds in Italy. Genotype E infection may differ from known genotypes since deletions of dUTPase and VPR proteins have been confirmed in different independent areas and goat breed, and play a key role on virus replication and pathogenesis. In particular, genotype E Roccaverano strain has been described as low pathogenic since does not lead to clinical symptoms in goats. In contrast, classical CAEV infected goats of the same area and breed presented arthritis. In this study, we have used intratracheal and intra-bone marrow routes to establish genotype E persistent infections. Humoral and cellular immune responses elicited in the host against genotype E and genotype B derived antigens were evaluated until 200 days post-inoculation. Compared to genotype B antigen, seroconversion against genotype E GAG P16-25 antigen was detected at 2-3 weeks after inoculation, significantly earlier and at higher titres. Interestingly, antibody avidity did not increase in the course of the experiment neither against P16-25 nor against SU5, both derived from genotype E. T cell proliferation against P25-GST fusion protein antigens derived from genotype E was firstly detected at 15 days post-inoculation and was maintained throughout time until week 20 post-infection, while T cell proliferation against the genotype B P25 was not produced by the end of the experiment at 20 weeks post-inoculation. The strength of reaction was also higher when using P25 E as stimulator antigen. In contrast with antibody and T cell proliferation, cytotoxic-T-lymphocyte (CTL) activity in the circulating lymphocytes (effector cells) using blood-derived macrophages (BDM) as target cells, was not strain specific being surprisingly higher against genotype B infected antigen presenting cells (APCs). This is the first study reporting experimentally induced immunological changes in SRLV genotype E infection and indicates that CTL activity may be the adaptive immune response able to induce protection against heterologous infection.
    Veterinary Immunology and Immunopathology 02/2011; 139(2-4):237-44. · 1.88 Impact Factor
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    ABSTRACT: The highly divergent, small ruminant lentivirus (SRLV) genotype E Roccaverano strain has a full genome consisting of 8,418 nucleotides, which lack the entire dUTPase subunit of the pol gene, the vpr-like accessory gene, and the 71-bp repeat of the U3 region within the long terminal repeat (LTR). These deletions affect in reverse transcriptase fidelity in non-dividing cells (dUTPase and vpr-like) and in the regulation of viral replication. Surprisingly, this SRLV strain was able to replicate efficiently in non-dividing cells (i.e., blood-derived macrophages), while replication in fibroblastic-like cells was somewhat restricted. To evaluate whether this observation was due to the presence/absence of specific transcription factors within these fibroblasts, U3 transcriptional activity was measured in the different cell types and revealed that both fibroblasts and macrophages were able to activate the viral promoter in the same manner. Among the transcription factor-binding sites present within the U3 region, the highly conserved Ap4 tandem repeat was shown to be sufficient for LTR promoter activity.
    Veterinary Research Communications 06/2010; 34 Suppl 1:S47-51. · 1.08 Impact Factor