CD34+ hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter activity. Studies also implicated the protein kinase A (PKA) pathway and the downstream transcription factor CREB-1 in interfacing with cAMP response elements located in the CXCR4 and viral promoter. These observations suggest that the cAMP signaling pathway may serve as a regulator of CXCR4 levels and concomitantly of HIV-1 replication in bone marrow (BM) progenitor cells.
Keyphrases
- antiretroviral therapy
- transcription factor
- hiv positive
- hiv infected
- bone marrow
- hiv testing
- human immunodeficiency virus
- poor prognosis
- protein kinase
- hepatitis c virus
- cell migration
- hiv aids
- binding protein
- men who have sex with men
- signaling pathway
- gene expression
- sars cov
- dna methylation
- south africa
- long non coding rna
- blood brain barrier
- dna binding
- induced apoptosis
- subarachnoid hemorrhage
- epithelial mesenchymal transition
- endoplasmic reticulum stress
- pi k akt
- immune response
- reactive oxygen species