Differential effects of HIV type 1 clade B and clade C Tat protein on expression of proinflammatory and antiinflammatory cytokines by primary monocytes

AIDS Res Hum Retroviruses. 2009 Jul;25(7):691-9. doi: 10.1089/aid.2008.0299.


The existence of multiple subtypes of HIV-1 worldwide has created new challenges to control HIV-1 infection and associated neuropathogenesis. Previous studies indicate a difference in neuropathogenic manifestations of HIV-1-associated neuroAIDS between clade B- and clade C-infected subjects with clade B being more neuropathogenic than clade C. However, the exact mechanism underlying the differences in the neuropathogenesis by both the subtypes remains elusive. Development of neuroAIDS is associated with a complex interplay between proinflammatory and antiinflammatory cytokines and chemokines. In the current study, we hypothesize that HIV-1 clade B and C Tat protein exert differential effects on human primary monocytes leading to differences in gene and protein expression of cytokines implicated in neuroAIDS. Primary human monocytes were treated with clade B and clade C Tat protein and quantitative real time PCR was performed to determine gene expression of proinflammatory cytokines (IL-6 and TNF-alpha) and antiinflammatory cytokines (IL-4 and IL-10). Further, cytokine secretion was measured in culture supernatants by ELISA, whereas intracellular cytokine expression was detected by flow cytometry. Results indicate that monocytes treated with Tat B showed significant upregulation of proinflammatory cytokines, IL-6 and TNF-alpha, as compared to Tat C-treated cultures. However, expression of antiinflammatory molecules and IL-4 and IL-10 was found to be higher in Tat C-treated compared to Tat B-treated cultures. Thus, our result shows for the first time that Tat B and Tat C differentially modulate expression of neuropathogenic molecules that may be correlated with the differences in neuroAIDS manifestation induced by clade-specific infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome / metabolism*
  • Acquired Immunodeficiency Syndrome / virology
  • Cell Culture Techniques
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • HIV-1* / genetics
  • HIV-1* / pathogenicity
  • Host-Pathogen Interactions
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Monocytes / metabolism*
  • Monocytes / virology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Virulence
  • tat Gene Products, Human Immunodeficiency Virus / physiology*


  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • tat Gene Products, Human Immunodeficiency Virus
  • Interleukin-10
  • Interleukin-4