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Quinolinic acid production is related to macrophage tropic isolates of HIV-1
B J Brew1, J Corbeil, L Pemberton
1Department of Neurology, St Vincent's Hospital, Sydney, Australia.
Abstract:
We sought to determine whether the neurotoxin quinolinic acid (QUIN) was produced by macrophages or lymphocytes infected with isolates of HIV-1 with varying degrees of macrophage tropism derived from patients with varying stages of AIDS dementia complex (ADC). Highly macrophage tropic isolates and minimally macrophage tropic isolates were used to inoculate macrophages and QUIN production was measured. Similarly, QUIN production from macrophages was monitored using a purified cell free highly macrophage tropic isolate and laboratory isolates SF33 and SF2. Each of these experiments was also performed with lymphocytes. We found that macrophages infected with macrophage tropic isolates of HIV-1 led to QUIN production while lymphocytes did not produce QUIN. The ability of the HIV-1 infected macrophages to produce QUIN was related to the viral inoculum and the degree of macrophage tropism of the isolate. The severity of ADC in the patient from whom a particular isolate was derived was not per se a determining factor for QUIN production. Purified cell free ADC isolates also led to QUIN production by macrophages thereby suggesting that HIV-1 infection alone is capable of inducing QUIN production.
Insights
HIV-1 infection of macrophages, not lymphocytes, produces the neurotoxin quinolinic acid (QUIN). Macrophage tropism of HIV-1 strains influences QUIN production, indicating HIV infection alone can induce this neurotoxin.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- HIV-1 infection can lead to neurological complications like AIDS dementia complex (ADC).
- Quinolinic acid (QUIN) is a neurotoxin implicated in neurodegenerative processes.
- The cellular source and regulation of QUIN production during HIV-1 infection are not fully understood.
Purpose of the Study:
- To investigate whether macrophages or lymphocytes produce quinolinic acid (QUIN) when infected with HIV-1.
- To determine the role of HIV-1 macrophage tropism and ADC severity in QUIN production.
Main Methods:
- Macrophages and lymphocytes were infected with HIV-1 isolates of varying macrophage tropism.
- QUIN production was measured in infected cells.
- Experiments utilized both patient-derived and laboratory HIV-1 isolates, including cell-free isolates.
Main Results:
- Macrophages infected with macrophage-tropic HIV-1 isolates produced QUIN, whereas lymphocytes did not.
- QUIN production correlated with viral inoculum and isolate macrophage tropism.
- Cell-free HIV-1 isolates also induced QUIN production in macrophages, suggesting HIV infection alone is sufficient.
Conclusions:
- HIV-1 infection of macrophages is the primary source of quinolinic acid (QUIN) production.
- Macrophage tropism of HIV-1 is a key factor in determining QUIN production.
- HIV-1 infection itself can induce QUIN production, independent of ADC severity.