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Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1 JR-FL in the setting of post-exposure prophylaxis in NOD/SCID/Jak3 -/- mice transplanted with human PBMCs.
- Source :
-
Antiviral research [Antiviral Res] 2018 Jan; Vol. 149, pp. 78-88. Date of Electronic Publication: 2017 Sep 08. - Publication Year :
- 2018
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Abstract
- Employing NOD/SCID/Jak3 <superscript>-/-</superscript> mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1 <subscript>JR-FL</subscript> (HIV <subscript>mC</subscript> ), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIV <subscript>mC</subscript> enabled us to visually locate infection foci and to examine the early dynamics of HIV <subscript>mC</subscript> infection without using a large amount of antiretroviral unlike in non-human primate models. Although when raltegravir (RAL) administration was begun 1 day after intraperitoneal (ip) inoculation of HIV <subscript>mC</subscript> , no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJ <subscript>mC</subscript> <superscript>RAL+</superscript> ) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJ <subscript>mC</subscript> (hNOJ <subscript>mC</subscript> <superscript>RAL-</superscript> ) mice became positive for p24 and pRNA and had significantly swollen lymph nodes in peritoneal cavity and abundant p24 <superscript>+</superscript> /mC <superscript>+</superscript> /CD3 <superscript>+</superscript> /CD4 <superscript>+</superscript> T cells and p24 <superscript>+</superscript> /mC <superscript>+</superscript> /CD68 <superscript>+</superscript> monocytes/macrophages were identified in their omenta and mesenteric lymphoid tissues/lymph nodes upon necropsy of the mice on day 14. In 12 hNOJ <subscript>mC</subscript> <superscript>RAL+</superscript> mice, no significantly swollen lymph nodes were seen compared to hNOJ <subscript>mC</subscript> <superscript>RAL-</superscript> mice; however, in the omentum of the 2 hNOJ <subscript>mC</subscript> <superscript>RAL+</superscript> mice that were positive for pRNA and in site RNA, mC <superscript>+</superscript> /p24 <superscript>+</superscript> /CD3 <superscript>+</superscript> /CD83 <superscript>+</superscript> cells were identified, suggesting that viral breakthrough occurred later in the observation period. The present data suggest that the use of hNOJ mouse model and HIV <subscript>mC</subscript> may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.<br /> (Copyright © 2017. Published by Elsevier B.V.)
- Subjects :
- Animals
Disease Models, Animal
Gene Expression
Genes, Reporter
Genetic Vectors genetics
HIV Infections drug therapy
HIV Infections prevention & control
HIV-1 genetics
Humans
Immunohistochemistry
Janus Kinase 3 deficiency
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear virology
Luminescent Proteins genetics
Mice
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Viral Load
Red Fluorescent Protein
Anti-HIV Agents pharmacology
HIV Infections virology
HIV-1 drug effects
Post-Exposure Prophylaxis methods
Raltegravir Potassium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 149
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 28893602
- Full Text :
- https://doi.org/10.1016/j.antiviral.2017.09.003