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Các mạch phản hồi pro-inflammatory xác định các phản ứng miễn dịch đối với nhiễm Lentivirus gây bệnh
Tóm tắt
Virus gây suy giảm miễn dịch ở người (HIV) thuộc họ Lentivirus gây ra tình trạng viêm mãn tính và AIDS ở người, với tỷ lệ tiến triển bệnh biến đổi giữa các cá nhân do cả các yếu tố từ chủ thể và virus. Tương tự, các virus lentivirus từ khỉ cũng có độ độc lực khác nhau dựa trên đặc điểm của cả loài chủ và chủng virus, tuy nhiên, các cơ chế miễn dịch dẫn đến độ độc lực khác nhau của Lentivirus vẫn chưa được hiểu một cách đầy đủ. Chúng tôi đã phân tích phản ứng miễn dịch trong một mô hình đặc biệt về độ độc lực của lentivirus, trong đó khỉ macaque đuôi lợn bị nhiễm các biến thể SIV có gen tương đồng cao nhưng khác biệt về độ độc lực. Chúng tôi áp dụng công nghệ transcriptomics đơn bào theo chiều dọc cho nhóm nghiên cứu này, cùng với các kỹ thuật liên lạc giữa các tế bào có độ phân giải đơn bào, nhằm hiểu các cơ chế miễn dịch ẩn giấu phía sau độ độc lực của lentivirus. So với một biến thể lentivirus có độc lực tối thiểu, nhiễm biến thể có độc lực cao dẫn đến sự kích hoạt các con đường viêm diễn ra chậm hơn, rộng hơn và kéo dài hơn, bao gồm một dấu hiệu interferon toàn cầu phong phú. Ngược lại, các tế bào đơn lẻ bị nhiễm Lentivirus có độc lực cao đã tăng cường ít gen được kích thích bởi interferon với cường độ thấp hơn, cho thấy rằng Lentivirus có độc lực cao đã tiến hóa để một phần thoát khỏi phản ứng interferon. Hơn nữa, chúng tôi xác định CXCL10 và CXCL16 là những yếu tố phân tử quan trọng điều khiển các con đường viêm phản ứng đặc biệt đối với nhiễm Lentivirus có độc lực cao. Các phản ứng miễn dịch đối với nhiễm Lentivirus có độc lực cao được đặc trưng bởi việc khuếch đại các mạch điều hòa các cytokine pro-inflammatory với kết nối theo chiều dọc dày đặc. Công trình của chúng tôi trình bày một mô hình về độ độc lực của lentivirus, nơi các thất bại trong các cơ chế kiểm soát virus giai đoạn đầu dẫn đến các mạch pro-inflammatory kéo dài, duy trì và khuếch đại, điều này tiếp tục thúc đẩy sự tiến triển của bệnh.
Từ khóa
#Lentivirus #HIV #phản ứng miễn dịch #cytokine #viêm #điều hòa #kiểm soát virus.Tài liệu tham khảo
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