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Updated: Jun 10, 2026
A Rat Model of EcoHIV Brain Infection
Published on: January 21, 2021
M-tropic HIV envelope protein gp120 exhibits a different neuropathological profile than T-tropic gp120 in rat
Alessia Bachis1, Maria I Cruz, Italo Mocchetti
1Department of Neuroscience, Georgetown University Medical Center, New Research Building, 3970 Reservoir Rd, Washington, DC 20057, USA.
Abstract:
Most early human immunodeficiency virus type 1 (HIV-1) strains are macrophage (M)-tropic HIV variants and use the chemokine receptor CCR5 for infection. Neuronal loss and dementia are less severe among individuals infected with M-tropic strains. However, after several years, the T-cell (T)-tropic HIV strain, which uses the CXCR4 variant, can emerge in conjunction with brain abnormalities, suggesting strain-specific differences in neuropathogenicity. The molecular and cellular mechanisms of such diversity remain under investigation. We have previously demonstrated that HIV envelope protein gp120IIIB, which binds to CXCR4, causes neuronal apoptosis in rodents. Thus, we have used a similar experimental model to examine the neurotoxic effects of M-tropic gp120BaL. gp120BaL was microinjected in the rat striatum and neuronal apoptosis was examined in the striatum, as well as in anatomically connected areas, such as the somatosensory cortex and the substantia nigra. gp120BaL promoted neuronal apoptosis and tissue loss that were confined to the striatum. Apoptosis was associated with microglial activation and increased levels of interleukin-1beta. Intriguingly, gp120BaL increased brain-derived neurotrophic factor in the striatum. Overall, our data show that gp120BaL demonstrates a different neuropathological profile than gp120IIIB. A better understanding of the pathogenic mechanisms mediating HIV neurotoxicity is vital for developing effective neuroprotective therapies against AIDS-associated dementia complex.
Insights
Macrophage-tropic HIV-1 envelope protein gp120BaL causes striatal neuronal apoptosis and tissue loss, unlike T-tropic variants. This finding is crucial for understanding HIV neurotoxicity and developing treatments for AIDS-associated dementia.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Early human immunodeficiency virus type 1 (HIV-1) strains are macrophage (M)-tropic, utilizing CCR5 and causing less severe dementia.
- Later T-cell (T)-tropic strains emerge, using CXCR4, and are associated with brain abnormalities, indicating strain-specific neuropathogenicity.
- Previous studies showed HIV envelope protein gp120IIIB (CXCR4-binding) induces neuronal apoptosis in rodents.
Purpose of the Study:
- To investigate the neurotoxic effects of M-tropic gp120BaL in a rodent model.
- To compare the neuropathological profile of M-tropic gp120BaL with that of T-tropic gp120IIIB.
Main Methods:
- Microinjection of gp120BaL into the rat striatum.
- Examination of neuronal apoptosis in the striatum and connected areas (somatosensory cortex, substantia nigra).
- Analysis of microglial activation, interleukin-1beta, and brain-derived neurotrophic factor (BDNF) levels.
Main Results:
- gp120BaL induced neuronal apoptosis and tissue loss specifically within the striatum.
- Apoptosis was accompanied by microglial activation and elevated interleukin-1beta.
- gp120BaL also increased BDNF levels in the striatum.
Conclusions:
- M-tropic gp120BaL exhibits a distinct neuropathological profile compared to T-tropic gp120IIIB.
- Understanding these strain-specific pathogenic mechanisms is vital for developing neuroprotective therapies against AIDS-associated dementia complex.
