Host Immune Responses That Promote Initial HIV Spread
Abstract
The host inflammatory response to HIV invasion is a necessary component of the innate antiviral activity that vaccines and early interventions seek to exploit/enhance. However the response is dependent on CD4+ T-helper cell 1 (Th1) recruitment and activation. It is this very recruitment of HIV-susceptible target cells that is associated with the initial viral proliferation. Hence, global enhancement of the inflammatory response by T-cells and dendritic cells will likely feed viral propagation. Mucosal entry sites contain inherent pathways, in the form of natural regulatory T-cells (nTreg), that globally dampen the inflammatory response. We created a model of this inflammatory response to virus as well as inherent nTreg-mediated regulation of Th1 recruitment and activation. With simulations using this model we sought to address the net effect of nTreg activation and its specific functions as well as identify mechanisms of the natural inflammatory response that are best targeted to inhibit viral spread without compromising initial antiviral activity. Simulation results provide multiple insights that are relevant to developing intervention strategies that seek to exploit natural immune processes: (1) induction of the regulatory response through nTreg activation expedites viral proliferation due to viral production by nTreg itself and not to reduced Natural Killer (NK) cell activity; (2) at the same time, induction of the inflammation response through either DC activation or Th1 activation expedites viral proliferation; (3) within the inflammatory pathway, the NK response is an effective controller of viral proliferation while DC-mediated stimulation of T-cells is a significant driver of viral proliferation; and (4) nTreg-mediated DC deactivation plays a significant role in slowing viral proliferation by inhibiting T-cell stimulation, making this function an aide to the antiviral immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA556930
Entities
People
- G. Dean
- H. Thomas Banks
- K. Wendelsdorf
- S. Nordone
- Shuhua Hu
Organizations
- Virginia Tech