Transcriptional gene silencing limits CXCR4-associated depletion of bone marrow CD34+ cells in HIV-1 infection

AIDS
Tetsuo Tsukamoto

Abstract

Hematological abnormalities that include changes in bone marrow, such as in anemia and pancytopenia, are common among HIV-infected patients, particularly in the advanced stage of disease. Such abnormalities may be caused by a reduced bone marrow function for hematopoiesis. The aim of this study was to determine whether transcriptional gene silencing can help to preserve the hosts' hematopoietic potential in addition to peripheral CD4+ T cells against CCR5-tropic HIV infection. NOD/SCID/JAK3null (NOJ) mice were transplanted with human cord-derived CD34+ cells with or without transduction with a lentiviral vector expressing a promoter-targeting shRNA called PromA. At 16 weeks after transplantation, mice engrafted with CD34+ cells were infected with CCR5-tropic HIV-1JRFL. At week 2 postinfection, HIV replication was observed in peripheral blood mononuclear cells and splenocytes. In mice transplanted with unmanipulated CD34+ cells, viral replication was accompanied by a loss of peripheral/spleen CD4+CCR5+ T cells. Interestingly, bone marrow CD34+ cells in HIV-infected mice were also depleted, but in a CXCR4-associated manner. Conversely, the lentiviral transfer of PromA in CD34+ cells prior to transplantation rendered the humanized...Continue Reading

References

Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·H MiyoshiI M Verma
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·N UchidaI L Weissman
Jan 30, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Heidi G W LimAnthony D Kelleher
May 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Antonella IsgròIvano Mezzaroma
Jun 4, 2008·The Journal of Biological Chemistry·Kazuo SuzukiAnthony D Kelleher
Feb 24, 2009·Microbes and Infection·Makoto YamagishiToshiki Watanabe
Jan 21, 2011·Virology·Scott G KitchenDong Sung An
Mar 16, 2011·Cell Host & Microbe·Christoph C CarterKathleen L Collins
Jun 26, 2013·Mediterranean Journal of Hematology and Infectious Diseases·Sharad A Dhurve, Alka S Dhurve
Jul 28, 2013·Blood·Christopher C NixonJerome A Zack
Dec 5, 2013·Molecular Therapy. Nucleic Acids·Kazuo SuzukiAnthony D Kelleher
Oct 7, 2015·Frontiers in Immunology·Chantelle L AhlenstielAnthony D Kelleher
Oct 28, 2015·Molecular Therapy. Nucleic Acids·Chantelle AhlenstielKazuo Suzuki
Mar 22, 2016·Scientific Reports·Mariluz AraíngaHoward E Gendelman
Apr 10, 2016·Nucleic Acids Research·Marc S Weinberg, Kevin V Morris

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Citations

Mar 11, 2020·Frontiers in Cellular and Infection Microbiology·Tetsuo Tsukamoto
Feb 25, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Junpeng ZhaoLunan Wang
Sep 15, 2020·Frontiers in Cellular and Infection Microbiology·Chantelle L AhlenstielAnthony D Kelleher
Nov 11, 2020·Current Opinion in Pharmacology·Anthony D KelleherChantelle L Ahlenstiel
Apr 4, 2021·Life Sciences·Mohsen SheykhhasanMassoud Saidijam

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