Journal of Antivirals & Antiretrovirals
Open Access
ISSN: 1948-5964
+44 1300 500008
ISSN: 1948-5964
+44 1300 500008
Santhi Gorantla
University of Nebraska Medical Center, USA
Posters-Accepted Abstracts: J Antivir Antiretrovir
Background: Understanding the role-played by HIV-1 clades in viral transmission and disease pathobiology remains far from complete. NOD/scid-IL-2R�?³c null (NSG) mice reconstituted with functional human immune system allows for productive longterm viral infection and associated immune and central nervous system pathologies. Thus, humanized NSG mice were used to assess clade-specific differences in viral virulence, cytopathicity and neurotoxicity. Methods: NSG mice (reconstituted at birth with human CD34+ stem cells) were infected either with HIV-1 clade B or C strains. Blood viral load (VL), CD4 and CD8 T cell numbers, and markers of immune activation were assessed. Brains were collected for quantitative immunohistology and neuropathologic tests. Results: Evidence of high viral replication and slower CD4+ T cell depletion rate was observed in clade C infections. T cell activation (CD4+CD38+) was notably higher in clade C, while T cell exhaustion (CD4+PD-1+) was lower in clade C correlating to higher number CD4+Ki67+ cells in spleen. Increased immune cell infiltration into the brains of mice with infection was observed with higher rates and extent of meningitis in clade C infected mice (C60 vs. B40%). Incidence of neuropathology in different regions of brain was comparable amongst both clades. Conclusion: Higher immune activation and T cell replication status in clade C infection might be contributing to both slower rate of CD4+ T cell depletion and brain immune cell infiltration. Humanized mice can be used to provide important insights and explanations needed to understand the disparities seen in viral transmission rate and HAND incidence in different HIV-1 clades.
Email: sgorantla@unmc.edu