8D3B

Hexameric HIV-1 (M-group) Q50Y/R120 mutant

8D3B の概要

• エントリーDOI: 10.2210/pdb8d3b/pdb
• 分子名称: Capsid protein p24 (1 entity in total)
• 機能のキーワード: capsid, viral protein
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 153921.07

構造登録者

Jacques, D.A.,Govasli, M.L.,Pinotsis, N.,James, L.C. (登録日: 2022-06-01, 公開日: 2022-10-19, 最終更新日: 2024-11-06)

主引用文献

Zuliani-Alvarez, L.,Govasli, M.L.,Rasaiyaah, J.,Monit, C.,Perry, S.O.,Sumner, R.P.,McAlpine-Scott, S.,Dickson, C.,Rifat Faysal, K.M.,Hilditch, L.,Miles, R.J.,Bibollet-Ruche, F.,Hahn, B.H.,Boecking, T.,Pinotsis, N.,James, L.C.,Jacques, D.A.,Towers, G.J.
Evasion of cGAS and TRIM5 defines pandemic HIV.
Nat Microbiol, 7:1762-1776, 2022

PubMed Abstract: Of the 13 known independent zoonoses of simian immunodeficiency viruses to humans, only one, leading to human immunodeficiency virus (HIV) type 1(M) has become pandemic, causing over 80 million human infections. To understand the specific features associated with pandemic human-to-human HIV spread, we compared replication of HIV-1(M) with non-pandemic HIV-(O) and HIV-2 strains in myeloid cell models. We found that non-pandemic HIV lineages replicate less well than HIV-1(M) owing to activation of cGAS and TRIM5-mediated antiviral responses. We applied phylogenetic and X-ray crystallography structural analyses to identify differences between pandemic and non-pandemic HIV capsids. We found that genetic reversal of two specific amino acid adaptations in HIV-1(M) enables activation of TRIM5, cGAS and innate immune responses. We propose a model in which the parental lineage of pandemic HIV-1(M) evolved a capsid that prevents cGAS and TRIM5 triggering, thereby allowing silent replication in myeloid cells. We hypothesize that this capsid adaptation promotes human-to-human spread through avoidance of innate immune response activation.

PubMed: 36289397
DOI: 10.1038/s41564-022-01247-0

実験手法

X-RAY DIFFRACTION (3.3 Å)