HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein

Jenny Shrestha, Maryline Santerre, Charles N.S. Allen, Sterling P. Arjona, Carmen Merali, Ruma Mukerjee, Kumaraswamy Naidu Chitrala, Jin Park, Asen Bagashev, Viet Bui, Eliseo A. Eugenin, Salim Merali, Marcus Kaul, Jeannie Chin, Bassel E. Sawaya

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


HIV-associated neurocognitive disorders (HAND) remain an unsolved problem that persists despite using antiretroviral therapy. We have obtained data showing that HIV-gp120 protein contributes to neurodegeneration through metabolic reprogramming. This led to decreased ATP levels, lower mitochondrial DNA copy numbers, and loss of mitochondria cristae, all-important for mitochondrial biogenesis. gp120 protein also disrupted mitochondrial movement and synaptic plasticity. Searching for the mechanisms involved, we found that gp120 alters the cyclic AMP response element-binding protein (CREB) phosphorylation on serine residue 133 necessary for its function as a transcription factor. Since CREB regulates the promoters of PGC1α and BDNF genes, we found that CREB dephosphorylation causes PGC1α and BDNF loss of functions. The data was validated in vitro and in vivo. The negative effect of gp120 was alleviated in cells and animals in the presence of rolipram, an inhibitor of phosphodiesterase protein 4 (PDE4), restoring CREB phosphorylation. We concluded that HIV-gp120 protein contributes to HAND via inhibition of CREB protein function.

Original languageEnglish (US)
Article number811481
JournalFrontiers in Aging Neuroscience
StatePublished - May 9 2022
Externally publishedYes


  • CREB protein
  • HIV
  • mitochondria
  • neurodegeneration
  • rolipram

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience


Dive into the research topics of 'HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein'. Together they form a unique fingerprint.

Cite this