Basic Science Award

There remains a subset of HIV-infected patients who maintain undetectable plasma HIV RNA levels (elite controllers) that make up approximately 1% of the HIV-infected population. The mechanism for this unique status is the subject of intensive research, but remains unknown. The objective of this proposal is to determine how a set of six cytokines found to be elevated in the serum of HIV elite controllers influences viral replication and cellular activation.

There remains a subset of HIV-infected patients who maintain undetectable plasma HIV RNA levels (elite controllers) that make up approximately 1% of the HIV-infected population. The mechanism for this unique status is the subject of intensive research, but remains unknown. The objective of this proposal is to determine how a set of six cytokines found to be elevated in the serum of HIV elite controllers influences viral replication and cellular activation.

The continuing spread of HIV/AIDS in people is predominantly fueled by sexual exposure to HIV-contaminated semen/seminal plasma (SP). SP harbors HIV infectivity enhancing factors that include at least two major classes of naturally occurring amyloid fibrils that promote virion attachment to cellular targets. SP also harbors a variety of pro-inflammatory factors that can indirectly facilitate HIV transmission by promoting the production of cytokines/chemokines that recruit permissive cells, enhance the translocation of HIV across the genital epithelium, and activate HIV gene transcription.

Sexual transmission accounts for most cases of HIV infection worldwide, with semen being the main carrier of viral particles during this process. Recent studies revealed that positively charged amyloid fibrils from human semen can substantially boost HIV infectivity rates. In two separate studies, M?nch et al. and our group identified two distinct HIV-enhancing semen amyloids.

The continuing spread of HIV/AIDS in people is predominantly fueled by sexual exposure to HIV-contaminated semen/seminal plasma (SP). SP harbors HIV infectivity enhancing factors that include at least two major classes of naturally occurring amyloid fibrils that promote virion attachment to cellular targets. SP also harbors a variety of pro-inflammatory factors that can indirectly facilitate HIV transmission by promoting the production of cytokines/chemokines that recruit permissive cells, enhance the translocation of HIV across the genital epithelium, and activate HIV gene transcription.

Sexual transmission accounts for most cases of HIV infection worldwide, with semen being the main carrier of viral particles during this process. Recent studies revealed that positively charged amyloid fibrils from human semen can substantially boost HIV infectivity rates. In two separate studies, M?nch et al. and our group identified two distinct HIV-enhancing semen amyloids.

Invariant natural killer T (NKT) cells are innate-like T cells that respond to lipid antigens presented on the MHC class I-like molecule CD1d. These immunoregulatory cells have the capacity for abundant cytokine release almost immediately after antigen recognition and are essential for the activation of multiple arms of the immune response, including dendritic cells, conventional T cells and B cells. Murine studies have shown that the intestinal microbiome is an important factor in the maturation of functional NKT cells.

Detection of gene expression by flow cytometry is currently limited to transcripts that are abundantly expressed, however the recently reported RNAscope technology offers greatly improved sensitivity and specificity and has the potential to change the approach to single-cell transcript measurements that currently require low sensitivity approaches and are extremely low throughput. As yet these probes have not been utilized for study of patient samples by flow cytometry.

Invariant natural killer T (NKT) cells are innate-like T cells that respond to lipid antigens presented on the MHC class I-like molecule CD1d. These immunoregulatory cells have the capacity for abundant cytokine release almost immediately after antigen recognition and are essential for the activation of multiple arms of the immune response, including dendritic cells, conventional T cells and B cells. Murine studies have shown that the intestinal microbiome is an important factor in the maturation of functional NKT cells.

Detection of gene expression by flow cytometry is currently limited to transcripts that are abundantly expressed, however the recently reported RNAscope technology offers greatly improved sensitivity and specificity and has the potential to change the approach to single-cell transcript measurements that currently require low sensitivity approaches and are extremely low throughput. As yet these probes have not been utilized for study of patient samples by flow cytometry.