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Frequency of Human CD45+ Target Cells is a Key Determinant of Intravaginal HIV-1 Infection in Humanized Mice.
- Source :
-
Scientific reports [Sci Rep] 2017 Nov 10; Vol. 7 (1), pp. 15263. Date of Electronic Publication: 2017 Nov 10. - Publication Year :
- 2017
-
Abstract
- Approximately 40% of HIV-1 infections occur in the female genital tract (FGT), primarily through heterosexual transmission. FGT factors determining outcome of HIV-1 exposure are incompletely understood, limiting prevention strategies. Here, humanized NOD-Rag1 <superscript>-/-</superscript> γc <superscript>-/-</superscript> mice differentially reconstituted with human CD34+ -enriched hematopoietic stem cells (Hu-mice), were used to assess target cell frequency and viral inoculation dose as determinants of HIV-1 infection following intravaginal (IVAG) challenge. Results revealed a significant correlation between HIV-1 susceptibility and hCD45+ target cells in the blood, which correlated with presence of target cells in the FGT, in the absence of local inflammation. HIV-1 plasma load was associated with viral dose at inoculation and frequency of target cells. Events following IVAG HIV-1 infection; viral dissemination and CD4 depletion, were not affected by these parameters. Following IVAG inoculation, HIV-1 titres peaked, then declined in vaginal lavage while plasma showed a reciprocal pattern. The greatest frequency of HIV-1-infected (p24+) cells were found one week post-infection in the FGT versus blood and spleen, suggesting local viral amplification. Five weeks post-infection, HIV-1 disseminated into systemic tissues, in a dose-dependent manner, followed by depletion of hCD45+ CD3+ CD4+ cells. Results indicate target cell frequency in the Hu-mouse FGT is a key determinant of HIV-1 infection, which might provide a useful target for prophylaxis in women.
- Subjects :
- Animals
Disease Models, Animal
Female
HIV Infections immunology
HIV Infections metabolism
HIV-1 immunology
Humans
Leukocyte Common Antigens immunology
Mice
Mice, Inbred NOD
Mice, Knockout
Vagina immunology
Vagina virology
HIV Infections transmission
HIV-1 metabolism
Leukocyte Common Antigens metabolism
Vagina metabolism
Viral Load
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29127409
- Full Text :
- https://doi.org/10.1038/s41598-017-15630-z