An Unusual Syncytia-Inducing Human Immunodeficiency Virus Type 1 Primary Isolate from the Central Nervous System that is Restricted to CXCR4, Replicates Efficiently in Macrophages, and Induces Neuronal Apoptosis
| Autor: | Linda D Starr-Spires, Joann Cutilli, Dennis L. Kolson, Ronald G. Collman, Ian Frank, Jerrold Sulcove, Yanjie Yi, Anjali Singh, Wei Chen |
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| Rok vydání: | 2003 |
| Předmět: |
Receptors
CXCR4 AIDS Dementia Complex Molecular Sequence Data Clone (cell biology) Apoptosis Biology Giant Cells Virus Cellular and Molecular Neuroscience Chemokine receptor Viral Envelope Proteins Virology medicine Humans Macrophage Amino Acid Sequence Primary isolate Tropism Neurons Syncytium Microglia Macrophages virus diseases medicine.anatomical_structure Neurology HIV-1 Neurology (clinical) |
| Zdroj: | Journal of Neurovirology. 9:432-441 |
| ISSN: | 1538-2443 1355-0284 |
| Popis: | Macrophage/microglia cells are the principal targets for human immunodeficiency virus type 1 (HIV-1) in the central nervous system (CNS). Prototype HIV-1 isolates from the CNS are macrophage (M)-tropic, non-syncytia-inducing (NSI), and use CCR5 for entry (R5 strains), but whether syncytia-inducing (SI) CXCR4-using X4 strains might play a role in macrophage/microglia infection and neuronal injury is unknown. To explore the range of features among HIV-1 primary isolates from the CNS, the authors analyzed an HIV-1 strain (TYBE) from cerebrospinal fluid of an individual with acquired immunodeficiency syndrome (AIDS) that was unusual because it was SI. Like other CNS isolates, HIV-1/TYBE replicated to high level in primary human macrophages, but, in contrast to CNS prototypes, TYBE used CXCR4 exclusively to infect macrophages. A functional TYBE env clone confirmed the X4 phenotype and displayed a highly charged V3 sequence typical of X4 strains. Supernatant from TYBE-infected primary human macrophages induced apoptosis of neurons. Thus, TYBE represents a novel type of CNS-derived HIV-1 isolate that is CXCR4-restricted yet replicates efficiently in macrophages and induce neuronal injury. These results demonstrate that HIV-1 variants in the CNS may possess a broader range of biological characteristics than generally appreciated, raise the possibility that X4 strains may participate in AIDS neuropathogenesis, and provide a prototype clade B HIV-1 strain that replicates efficiently in primary macrophages through the exclusive use of CXCR4 as a coreceptor. |
| Databáze: | OpenAIRE |
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