title: Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats.
abstract: Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection. In this study, we analyse two goat populations within the same herd, harbouring low or high proviral SRLV loads respectively, both showing a robust antibody response. In vivo findings were confirmed in vitro since fibroblastic cell lines obtained from one high and one low proviral load representative goats, showed respectively a high and a faint production of virus upon infection with reference and field circulating SRLV strains. Differences in virus production were relieved when strain CAEV-Co was used for experimental infection. We analysed LTR promoter activity, proviral load, entry step and production of virus and viral proteins. Intriguingly, proteasomal activity was higher in fibroblasts from low proviral load animals and proteasome inhibition increased viral production in both cell lines, suggesting the implication of active proteasome-dependent restriction factors. Among them, we analysed relative expression and sequences of TRIM5α, APOBEC3 (Z1, Z2, Z3 and Z2-Z3) and BST-2 (Tetherin) and found a global antiviral status in low proviral carriers that may confer protection against viral shedding and disease onset.
authors.affiliation: Instituto de Agrobiotecnología, UPNA-CSIC-Gob, de Navarra, Avda. Pamplona 123, 31192 Mutilva, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Crespo
authors.affiliation: Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, L.go P. Braccini 2, 10095 Grugliasco (TO), Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bertolotti
authors.affiliation: Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, L.go P. Braccini 2, 10095 Grugliasco (TO), Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Proffiti
authors.affiliation: Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, L.go P. Braccini 2, 10095 Grugliasco (TO), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cascio
authors.affiliation: Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, L.go P. Braccini 2, 10095 Grugliasco (TO), Italy.
authors.forename: Fulvia
authors.initials: F
authors.lastname: Cerruti
authors.affiliation: Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Torino, Italy.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Acutis
authors.affiliation: Instituto de Agrobiotecnología, UPNA-CSIC-Gob, de Navarra, Avda. Pamplona 123, 31192 Mutilva, Spain.
authors.forename: Damián
authors.initials: D
authors.lastname: de Andrés
authors.affiliation: Instituto de Agrobiotecnología, UPNA-CSIC-Gob, de Navarra, Avda. Pamplona 123, 31192 Mutilva, Spain. Electronic address: ramses.reina@unavarra.es.
authors.forename: Ramsés
authors.initials: R
authors.lastname: Reina
authors.affiliation: Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, L.go P. Braccini 2, 10095 Grugliasco (TO), Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosati
mesh_terms: D000071478:APOBEC Deaminases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D015511:Goat Diseases / Q000821:virology*; D006041:Goats; D006801:Humans; D016086:Lentivirus / Q000145:classification* / Q000235:genetics; D016180:Lentivirus Infections / Q000662:veterinary* / Q000821:virology; D011533:Proviruses; D011687:Purines; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D017201:Virus Shedding
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; C569692:PH006 compound; D011687:Purines; D014764:Viral Proteins; D000071478:APOBEC Deaminases
keywords: APOBEC3; Long-term non-progressors; Proviral load; Small ruminant lentivirus; TRIM5α; Tetherin