1. English audio file (mp3 format, 23.8 MB)

Key findings presented in this session included the observation that decreased susceptibility to both HIV and SIV-related disease may correlate with a "dampened" innate immune response, and that genital herpes is associated  with elevated HIV target cells in the genital tract, even in the absence of herpes reactivation.

WEAA0301: Blake Ball (Canada)

• Studies of HIV resistant sex workers from Pumwani
• Saw less IFNg response to stimulation of lymphocytes by TLR ligands or LPS
• Also HIGHER IL10 responses
• Comment was made that this correlated with primate data, in which pre-exposure TLR stimulation in the genital tract was associated with a higher VL post challenge
• OVERALL - less inflammatory innate immune response may be associated with lower HIV susceptibility

WEAA0302: Joseph Barbercheck (USA)

• Studied T reg cells in SIV+ and SIV- macaques
• Defined T regs as FoxP3+ - was exclusively expressed by CD3+ CD4+ CD25+ cells
• These cells inhibited the proliferation of conventional T cells, in a dose dependent way
• Tregs at baseline were less common in the gut of Rhesus monkeys (a pathogenic SIV model) compared to AGMs (a nonpathogenic model)
• After infection, a very early induction of Treg response was seen in the gut of AGMs, correlating with a lack of immune stimulation and increased levels of antiinflammatory cytokines (IL10)
• Also Tregs populations were better preserved in AGM chronic infection, perhaps explaining lack of immune activation.
• OVERALL - early T regs may dampen inflammation and prevent immunopathogenesis in these primate models

WEAA0303: Angela Meier (USA)

• Many new TLR7/8 ligands mapped in the RNA of HIV LTR
• Looked at purified CD8 T cells, which were seen to express most TLRs
• CD8 T cells were activated by ssRNA40, a TLR ligand from HIV
• Also, several other ssRNA sequences were mapped in HIV that activate TLR7/8 and induce CD69 upregulation (cell activation)
• Activation was indirect, and needed CD14+ cells to act as APCs, as well as direct cell-cell contact – do not know nature of the indirect signalling
• OVERALL - HIV encodes several ligands that can activate TLRs and inflammation, perhaps contributing to immunopathogenesis

WEAA0304: Anu Rebbapragada (Canada)

• Clinical interaction between HIV and HSV2 confirmed in Kenyan sex workers – HIV infected women more likely to be HSV2 positive, and to shed HSV2
• HSV2 infection in HIV negative women was associated with a three-fold increase in cervical CCR5+ CD4+ T cells, and with a ten-fold increase in DC-SIGN+ iDCs
• All this was in the absence of either clinical or virological HSV2 reactivation
• OVERALL - even without ulcers or detectable herpes, HSV2 may increase HIV target cells in the genital tract

WEAA0305: S. Tugisov (USA)

• Transcytosis is a way for HIV to cross mucosal membranes
• These investigators made a model of the oral epithelium and looked at the ability of X4 and R5 viruses to cross, and to cause infection
• Interestingly, cell free virus was not infectious after crossing the epithelium, while cell-associated virus maintained infectivity
• The mechanism is being investigated
• OVERALL - transcytosis of cell associated virus may be important in HIV transmission, although many questions remain

WEAA0304.  Potential mucosal immune mechanisms for increased HIV susceptibility in women infected by Herpes simplex type 2

Researchers shed further light on the dynamics of the mucosal immune protection and susceptability.  In one presentation, researchers in Canada and Kenya showed progress in defining the mechanisms by which HSV2 infection enhances susceptibility to HIV, and how HIV infection then increases HSV2 activation and shedding.  (Anu Rebbapragada)

Increased understanding about mucosal immunity and susceptability may contribute to development of microbicides and other HIV and STI prevention efforts.