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Long-term productive human immunodeficiency virus-1 infection in human infant microglia
J P Ioannidis1, S Reichlin, P R Skolnik
1Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Boston, MA 02111, USA.
Abstract:
The course of human immunodeficiency virus 1 (HIV-1) infection in human infant microglia was studied using purified primary cultures of microglia derived from brain autopsy tissue. Previous in vitro studies have used fetal or adult brain tissue. Important differences may exist between brain tissues of different maturational ages with regard to HIV-1 replication and other neuropathogenic effects. Infant microglia were infected with four different strains of HIV-1 (JR-FL, JR-CSF, Ba-L, and IIIB). Productive infection was demonstrated by p24 antigen production, immunocytochemistry, and recovery of replication-competent virus from the supernatants of the infected cultures. Multinucleated giant cells developed in culture mimicking the neuropathological changes seen in the brains of patients with HIV encephalopathy. Productive infection was more readily established by monocyte-tropic strains (JR-FL and Ba-L) of HIV-1 than by a lymphocyte-tropic strain (IIIB). p24 antigen production in this system peaked at 47 to 51 days postinfection. Viral persistence in giant cells was demonstrated by immunocytochemistry for the gp120 and gp41 viral antigens as late as 70 days postinfection. This in vitro culture system, using infant microglia that support viral replication for more than 2 months, may provide a useful model for studying the pathogenesis of progressive HIV encephalopathy.
Insights
Human infant microglia support human immunodeficiency virus 1 (HIV-1) replication for over two months, mimicking HIV encephalopathy. This study establishes a novel in vitro model for investigating HIV-1 neuropathogenesis.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Human immunodeficiency virus 1 (HIV-1) infection can cause neurological complications, including HIV encephalopathy.
- Previous in vitro studies on HIV-1 neuropathogenesis have primarily used fetal or adult brain tissue, potentially overlooking age-specific effects.
Purpose of the Study:
- To investigate the course of HIV-1 infection in primary cultures of human infant microglia.
- To establish an in vitro model using infant microglia to study HIV-1 neuropathogenesis.
Main Methods:
- Purified primary cultures of microglia were derived from infant brain autopsy tissue.
- Microglial cultures were infected with four different strains of HIV-1 (JR-FL, JR-CSF, Ba-L, and IIIB).
- Viral replication was assessed by p24 antigen production, immunocytochemistry, and virus recovery; neuropathological changes were observed.
Main Results:
- Infant microglia supported productive HIV-1 infection, evidenced by p24 antigen production and virus recovery.
- Monocyte-tropic HIV-1 strains (JR-FL, Ba-L) established infection more readily than the lymphocyte-tropic strain (IIIB).
- Multinucleated giant cells formed, mirroring neuropathological changes in HIV encephalopathy, with viral persistence observed for up to 70 days.
Conclusions:
- Human infant microglia support sustained HIV-1 replication and neuropathological changes in vitro.
- This infant microglia culture system provides a valuable model for studying the pathogenesis of progressive HIV encephalopathy.