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Evasion of cGAS and TRIM5 defines pandemic HIV

DOI: 10.1038/s41564-022-01247-0 DOI Help

Authors: Lorena Zuliani-Alvarez (University of California San Francisco; University College London) , Morten L. Govasli (University College London) , Jane Rasaiyaah (University College London) , Chris Monit (University College London) , Stephen O. Perry (University College London) , Rebecca P. Sumner (University College London) , Simon Mcalpine-Scott (University College London (UCL)) , Claire Dickson (UNSW Sydney) , K. M. Rifat Faysal (UNSW Sydney) , Laura Hilditch (University College London) , Richard J. Miles (University College London) , Frederic Bibollet-Ruche (University of Pennsylvania) , Beatrice H. Hahn (University of Pennsylvania) , Till Boecking (UNSW Sydney) , Nikos Pinotsis (Birkbeck College, University of London) , Leo C. James (MRC Laboratory of Molecular Biology) , David A. Jacques (UNSW Sydney) , Greg J. Towers (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 7 , PAGES 1762 - 1776

State: Published (Approved)
Published: November 2022
Diamond Proposal Number(s): 8547 , 11235

Open Access Open Access

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.

Diamond Keywords: Human Immunodeficiency Virus (HIV); Viruses

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: P13 at PETRA III

Added On: 02/11/2022 08:54


Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)