PT  - JOURNAL ARTICLE
AU  - Sizun Jiang
AU  - Chi Ngai Chan
AU  - Xavier Rovira-Clave
AU  - Han Chen
AU  - Yunhao Bai
AU  - Bokai Zhu
AU  - Erin McCaffrey
AU  - Noah F. Greenwald
AU  - Candace Liu
AU  - Graham L Barlow
AU  - Jason L. Weirather
AU  - John Paul Oliveria
AU  - Darci Philips
AU  - Nilanjan Mukherjee
AU  - Kathleen Busman-Sahay
AU  - Michael Nekorchuk
AU  - Margaret Terry
AU  - Skyler Younger
AU  - Marc Bosse
AU  - Janos Demeter
AU  - Yury Golstev
AU  - David Robert McIlwain
AU  - Michael Angelo
AU  - Jacob D. Estes
AU  - Garry P. Nolan
TI  - Virus-Dependent Immune Conditioning of Tissue Microenvironments
AID  - 10.1101/2021.05.21.444548
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.21.444548
4099  - http://biorxiv.org/content/early/2021/05/23/2021.05.21.444548.short
4100  - http://biorxiv.org/content/early/2021/05/23/2021.05.21.444548.full
AB  - A thorough understanding of complex spatial host-disease interactions in situ is necessary in order to develop effective preventative measures and therapeutic strategies. Here, we developed Protein And Nucleic acid IN situ Imaging (PANINI) and coupled it with Multiplexed Ion Beam Imaging (MIBI) to sensitively and simultaneously quantify DNA, RNA, and protein levels within the microenvironments of tissue compartments. The PANINI-MIBI approach was used to measure over 30 parameters simultaneously across large sections of archival lymphoid tissues from non-human primates that were healthy or infected with simian immunodeficiency virus (SIV), a model that accurately recapitulates human immunodeficiency virus infection (HIV). This enabled multiplexed dissection of cellular phenotypes, functional markers, viral DNA integration events, and viral RNA transcripts as resulting from viral infection. The results demonstrated immune coordination from an unexpected upregulation of IL10 in B cells in response to SIV infection that correlated with macrophage M2 polarization, thus conditioning a potential immunosuppressive environment that allows for viral production. This multiplexed imaging strategy also allowed characterization of the coordinated microenvironment around latently or actively infected cells to provide mechanistic insights into the process of viral latency. The spatial multi-modal framework presented here is applicable to deciphering tissue responses in other infectious diseases and tumor biology.Competing Interest StatementG.P.N. and M.A. are co-founders and have personal financial interests in the company IonPath, which manufactures the instrument used in this manuscript.