Advertisement

 

 

Frequency of Human CD45+ Target Cells is a Key Determinant of Intravaginal HIV-1 Infection in Humanized Mice.

Frequency of Human CD45+ Target Cells is a Key Determinant of Intravaginal HIV-1 Infection in Humanized Mice.
Author Information (click to view)

Nguyen PV, Wessels JM, Mueller K, Vahedi F, Anipindi V, Verschoor CP, Chew M, Deshiere A, Karniychuk U, Mazzulli T, Tremblay MJ, Ashkar AA, Kaushic C,


Nguyen PV, Wessels JM, Mueller K, Vahedi F, Anipindi V, Verschoor CP, Chew M, Deshiere A, Karniychuk U, Mazzulli T, Tremblay MJ, Ashkar AA, Kaushic C, (click to view)

Nguyen PV, Wessels JM, Mueller K, Vahedi F, Anipindi V, Verschoor CP, Chew M, Deshiere A, Karniychuk U, Mazzulli T, Tremblay MJ, Ashkar AA, Kaushic C,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Scientific reports 2017 11 107(1) 15263 doi 10.1038/s41598-017-15630-z

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(-/-) 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.

Submit a Comment

Your email address will not be published. Required fields are marked *

2 + 14 =

[ HIDE/SHOW ]