Frequency of Human CD45+ Target Cells is a Key Determinant of Intravaginal HIV-1 Infection in Humanized Mice.
Philip V NguyenJocelyn M WesselsKristen MuellerFatemeh VahediVarun AnipindiChris P VerschoorMarianne ChewAlexandre DeshiereUladzimir KarniychukTony MazzulliMichel J TremblayAli A AshkarCharu KaushicPublished in: Scientific reports (2017)
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-/- γc-/- 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.
Keyphrases
- antiretroviral therapy
- hiv infected
- induced apoptosis
- hiv positive
- human immunodeficiency virus
- cell cycle arrest
- hepatitis c virus
- hiv aids
- stem cells
- hiv testing
- sars cov
- endothelial cells
- endoplasmic reticulum stress
- single cell
- oxidative stress
- signaling pathway
- gene expression
- clinical trial
- type diabetes
- cell death
- cell therapy
- men who have sex with men
- metabolic syndrome
- south africa
- mesenchymal stem cells
- polycystic ovary syndrome
- pregnant women
- cell proliferation
- adipose tissue
- monoclonal antibody
- nk cells
- skeletal muscle