RT Journal Article
SR Electronic
T1 Macrophage activation of cGAS and TRIM5 distinguish pandemic and non-pandemic HIV
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.21.477263
DO 10.1101/2022.01.21.477263
A1 Lorena Zuliani Alvarez
A1 Morten L. Govasli
A1 Jane Rasaiyaah
A1 Chris Monit
A1 Stephen O. Perry
A1 Rebecca P. Sumner
A1 Simon McAlpine-Scott
A1 Claire Dickson
A1 K. M. Rifat Faysal
A1 Laura Hilditch
A1 Richard J. Miles
A1 Frederic Bibollet-Ruche
A1 Beatrice H. Hahn
A1 Till Boecking
A1 Nikos Pinotsis
A1 Leo C. James
A1 David A. Jacques
A1 Greg J. Towers
YR 2022
UL http://biorxiv.org/content/early/2022/01/22/2022.01.21.477263.abstract
AB Pandemic viruses remain a global threat to health and economics but how they adapt to become pandemic remains poorly understood. Here we compare pandemic HIV-1(M) and non-pandemic HIV-(O) and HIV-2 strains finding that non-pandemic HIV replicate poorly in myeloid cell models due to activation of cGAS and TRIM5, and ensuing antiviral responses. We use phylogenetics and viral capsid structural biology to define specific differences between pandemic and non-pandemic HIV capsids and demonstrate that their genetic reversal in HIV-1(M) mutants causes TRIM5, cGAS and innate immune activation. We propose a model in which the parental lineage of pandemic HIV-1(M) has uniquely evolved a dynamic capsid that avoids activation of cGAS and TRIM5 to establish cloaked replication in myeloid cells. The unique adaptations of the pandemic virus lineage suggests a role in effective human-to-human transmissibility and highlight the importance of avoiding innate immune activation during pandemic human-to-human viral transmission.Competing Interest StatementThe authors have declared no competing interest.