Maedi-visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and cofactor required for A3 degradation

The mammalian apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) family of cytidine deaminases restrict viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called Vif, which recruits A3 proteins to Cullin-RING E3 ubiquitin ligases such as Cul5 for ubiquitylation and subsequent proteasomal degradation. While Vif proteins from primate lentiviruses like HIV-1 utilize the transcription factor CBFβ as a non-canonical cofactor to stabilize the complex, maedi-visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Since CBFβ and CypA are both highly conserved among mammals, the requirement for two different cellular cofactors suggests that these two A3-targeting Vif proteins have different biochemical and structural properties. To investigate this topic, we used a combination of in vitro biochemical assays and in vivo A3 degradation assays to study motifs required for MVV Vif to bind zinc ion, Cul5, and the cofactor CypA. Our results demonstrate that while some common motifs between HIV-1 Vif and MVV Vif are involved in recruiting Cul5, different determinants in MVV Vif are required for cofactor binding and stabilization of the E3 ligase complex, such as the zinc-binding motif and N- and C-terminal regions of the protein. Results from this study advance our understanding of the mechanism of MVV Vif recruitment of cellular factors and the evolution of lentiviral Vif proteins.

Study results of diagnosis of Maedi-visna disease in sheep

In order to detect pathological and histopathological findings of Maedi-Visna disease, pulmonary tissues which had lesions and suspected of the lung disease were collected in slaughterhouses near Ulaanbaatar city, Batsumber soum of Tuv province, Ulziit soum of Dornogobi province. PCR was performed to examine the part of gene of Maedi-Visna virus and pulmonary tissue of one sheep was positive. Histopathological examination was conducted on lung and by microscopic investigation, interstitial inflammation and inclusion body in cytoplasm of the alveoli epithelium was determined on the sample as some specific findings of Maedi-Visna infection. Хонинд Маеди-висна өвчин оношилсон дүнгээс Маеди-Висна өвчний өөрчлөлтийг хонины уушгинд илрүүлэх зорилгоор Улаанбаатар хот орчмын мал нядалгааныгазрууд болон Төв аймгийн Батсүмбэр, Дорноговь аймгийн Өлзийт сумаас эмгэгтэй байж болзошгүй хонины уушгины эдийн дээжнүүд цуглуулав. Уушгины эдийн дээжүүдийг Полимеразын гинжин урвал (ПГУ)-аар шинжлэхэд нэг хонины уушгины эдэд тус өвчин үүсгэгчийн өвөрмөц гений хэсэг илэрсэн. Дээжинд хийсэн эмгэг судлал, бичил бүтцийн шинжилгээгээр Маеди-Висна өвчний үед гардаг өвөрмөц өөрчлөлтүүд болох уушгины завсрын эдийн үрэвсэл, цулцангийн ханын хучуур эсэд өвөрмөц оршихуун биенцэр үүссэн болох нь тогтоогдов. Түлхүүр үг: уушгины эд, үлэмж-, бичил өөрчлөлт, уушгины завсрын эдийн үрэвсэл, оршихуун биенцэр