When do models of NeuroAIDS faithfully imitate "the real thing"?

TitleWhen do models of NeuroAIDS faithfully imitate "the real thing"?
Publication TypeJournal Article
Year of Publication2018
AuthorsGelman, BB, Endsley, J, Kolson, D
JournalJ Neurovirol
Date Published2018 04
KeywordsAIDS Dementia Complex, Animals, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Antiretroviral Therapy, Highly Active, Antiviral Agents, Biomarkers, Brain, Central Nervous System, Cognitive Dysfunction, Cytokines, Disease Models, Animal, HIV-1, Humans, Neurotransmitter Agents, Platelet Endothelial Cell Adhesion Molecule-1, Receptors, Cell Surface, Synaptic Transmission, Ubiquitins, Virus Latency

HIV-infected patients treated with antiretroviral medicines (ART) still face neurological challenges. HIV-associated neurocognitive disturbances (HAND) can occur, and latent viral DNA persisting in the central nervous system (CNS) prevents eradication of HIV. This communication focuses on how to develop experimental models of HAND and CNS HIV latency that best imitate the CNS pathophysiology in diseased humans, which we take to be "the real thing." Models of HIV encephalitis (HIVE) with active CNS viral replication were developed in the early years of the AIDS pandemic. The clinical relevancy of such models is in sharp decline because HIVE seldom occurs in virally suppressed patients, while HAND remains common. The search for improved models of HAND should incorporate the neurochemical, neuroimmunological and neuropathological features of virally suppressed patients. Common anomalies in these patients as established in autopsy brain specimens include brain endothelial cell activation and neurochemical imbalances of synaptic transmission; classical neurodegeneration may not be as crucial. With regard to latent HIV with viral suppression, human brain specimens show that the pool of latent proviral HIV DNA in the CNS is relatively small relative to the total body pool and does not change substantially over years. The CNS pool of latent virus probably differs from lymphoid tissues, because the mononuclear phagocyte system sustains productive infection (versus lymphocytes). These and yet-to-be discovered aspects of the human CNS of virally suppressed patients need to be better defined and addressed in experimental models. To maintain clinical relevancy, models of HAND and viral latency should faithfully emulate "the real thing."

Alternate JournalJ Neurovirol
PubMed ID29256039
PubMed Central IDPMC5910470
Grant ListR01HL129881 / NH / NIH HHS / United States
R01MH104134 / NH / NIH HHS / United States
R01 MH104134 / MH / NIMH NIH HHS / United States
R01 NS072005 / NS / NINDS NIH HHS / United States
R01 MH095671 / MH / NIMH NIH HHS / United States
M01 RR000073 / RR / NCRR NIH HHS / United States
R01MH101017 / NH / NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
R01 MH111389 / MH / NIMH NIH HHS / United States
U24MH100930 / NH / NIH HHS / United States