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.

Small ruminant lentiviruses (SRLV) infect the monocyte/macrophage lineage inducing a long-lasting infection affecting body condition, production and welfare of sheep and goats all over the world. Macrophages play a pivotal role on the host’s innate and adaptative immune responses against parasites by becoming differentially activated. Macrophage heterogeneity can tentatively be classified into classically differentiated macrophages (M1) through stimulation with IFN-γ displaying an inflammatory profile, or can be alternatively differentiated by stimulation with IL-4/IL-13 into M2 macrophages with homeostatic functions. Since infection by SRLV can modulate macrophage functions we explored here whether ovine and caprine macrophages can be segregated into M1 and M2 populations and whether this differential polarization represents differential susceptibility to SRLV infection. We found that like in human and mouse systems, ovine and caprine macrophages can be differentiated with particular stimuli into M1/M2 subpopulations displaying specific markers. In addition, small ruminant macrophages are plastic since M1 differentiated macrophages can express M2 markers when the stimulus changes from IFN-γ to IL-4. SRLV replication was restricted in M1 macrophages and increased in M2 differentiated macrophages respectively according to viral production. Identification of the infection pathways in macrophage populations may provide new targets for eliciting appropriate immune responses against SRLV infection.

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.

18Genotype E of small ruminant lentivirus has been recently described in goats from different breeds 31T cell proliferation against p25-GST fusion protein antigens derived from genotype E was firstly 40This is the first study reporting experimentally induced immunological changes in SRLV genotype 41 E infection and indicates that CTL activity may be the adaptive immune response able to induce 42 protection against heterologous infection.

No abstract