Multiomics investigation revealing the characteristics of HIV-1-infected
cells in vivo

Date:
July 28, 2020
Source:
The Institute of Medical Science, The University of Tokyo
Summary:
A research group using HIV-1-infected cells performed
'multiomics' analyses, which are technologies recently developed to
comprehensively investigate the features of biological samples.In
this study, a hematopoietic stem cell-transplanted humanized
mouse model infected with a gene-modified HIV-1 was used to reveal
multiple characteristics of HIV- 1-producing cells in vivo.



FULL STORY ==========================================================================
For eradication of HIV-1 infection, it is important to elucidate the
detailed features and heterogeneity of HIV-1-infected cells in vivo. In
this study, a hematopoietic stem cell-transplanted humanized mouse
model infected with a gene-modified HIV-1 was used to reveal multiple characteristics of HIV-1- producing cells in vivo.


==========================================================================
A research group at The Institute of Medical Science, The University of
Tokyo (IMSUT) using HIV-1-infected cells performed "multiomics" analyses,
which are technologies recently developed to comprehensively investigate
the features of biological samples.

"Our findings describe multiple characteristics of HIV-1-producing
cells in vivo, which could provide clues for the development of an
HIV-1 cure.," said the lead scientist, Kei Sato, Associate Professor
(Principal Investigator) in the Division of Systems Virology, Department
of Infectious Disease Control, IMSUT.

The results of this research were published in Cell Reports on July
14, 2020.

Study for "HIV-1 cure" For eradication of HIV-1 infection, it is important
to gain an in-depth understanding of the wide-ranging characteristics
of HIV-1-infected cells in vivo.



========================================================================== Recently developed 'omics' analyses (*1) can be a powerful tool
to identify the characteristics of HIV-1-infected cells. However,
it should be noted that a large majority of the CD4+ T cells(*2) in
infected individuals are uninfected, and therefore, the transcriptional profiles of "bulk" CD4+ T cells in vivo do not reflect those of "pure" HIV-1-producing cells.

Multiomics analysis to comprehensively reveal the features of
HIV-1-infected cells in vivo In this study, the research group used a
human hematopoietic stem cell- transplanted humanized mouse model that maintains human leukopoiesis under relatively stable immunological
conditions in vivo and a replication-competent reporter HIV-1, and
used four recently developed techniques to investigate viral genomics
and transcriptomics.

According to the research group, this study consisted of the four
following analyses: First, droplet digital PCR revealed the presence
of potential reservoirs in infected humanized mice. Second, ligation
mediated PCR showed the preference of HIV-1 to integrate into open
chromatin regions, as suggested by the association of the epigenetic modifications of integration sites with viral production.

Third, digital RNA-sequencing quantified the absolute copy number of
viral transcripts in the HIV-1-producing cells in vivo and further
identified the differentially expressed genes between virus-infected
and uninfected cells.

Finally, single-cell RNA-sequencing revealed and characterized the heterogeneity of the HIV-1-producing cells in vivo.



========================================================================== Associate Professor Sato emphasized "To our knowledge, this study is the
first investigation to describe multiple aspects of HIV-1-producing cells
and also the first comprehensive investigation of the characteristics
of HIV-1-infected cells in vivo" .

Notes(*1) 'omics' analyses A field of scientific study that aims to comprehensively characterize and quantify the feature of biological
samples. The combination of multiple biological "-ome" information
categories (e.g., genome and transcriptome).

(*2) CD4+ T cells An immune cell subset that orchestrates the acquired
immune response.

Funding This study was supported in part by AMED J-PRIDE (19fm0208006h0003
to Kei Sato), KAKENHI Scientific Research B (18H02662 to Kei Sato),
KAKENHI Scientific Research on Innovative Areas "Neovirology" (16H06429, 16K21723, 17H05813, 19H04826 to Kei Sato), JST CREST (to Kei Sato), JSPS KAKENHI PAGS 16H06279 (to K.Sato), AMED Research Program on HIV/AIDS 19fk0410014 (19fk0410014, 19fk0410019 to Yoshio Koyanagi and Kei Sato),
and JSPS Research Fellow (PD 19J01713 to Jumpei Ito).


========================================================================== Story Source: Materials provided by The_Institute_of_Medical_Science,_The_University_of Tokyo. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Hirofumi Aso, Shumpei Nagaoka, Eiryo Kawakami, Jumpei Ito,
Saiful Islam,
Benjy Jek Yang Tan, Shinji Nakaoka, Koichi Ashizaki, Katsuyuki
Shiroguchi, Yutaka Suzuki, Yorifumi Satou, Yoshio Koyanagi,
Kei Sato.

Multiomics Investigation Revealing the Characteristics of
HIV-1-Infected Cells In Vivo. Cell Reports, 2020; 32 (2): 107887
DOI: 10.1016/ j.celrep.2020.107887 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200728113625.htm

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