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Distinctive pattern of infection and replication of HIV1 strains in blood-derived macrophages
H Schmidtmayerova1, C Bolmont, S Baghdiguian
1Unité de Recherches INSERM U322 sur les Rétrovirus et Maladies Associées, Marseille, France.
Abstract:
The macrophage-tropic virus HIV1-PAR, isolated from cerebrospinal fluid of HIV1-seropositive man, induced cytopathic effect accompanied by different magnitude of the virus production in blood-derived macrophages (BDM) obtained from different donors. HIV1-PAR-specific RNA was detected by in situ hybridization in 15 and 66% of BDM producing low and high levels of virus, respectively. In contrast with HIV1-PAR, infection of BDM with two laboratory strains adapted to T-cell lines, HIV1-LAV prototype and HIV1-NDK, a Zairian virus that is highly cytopathic for T-lymphocytes, resulted in a low production of HIV1 p24gag in culture fluid. Expression of HIV1-LAV and HIV1-NDK RNA was detected by in situ hybridization in a maximum of 1% of macrophages. Only HIV1-NDK, and not HIV1-LAV, induced ultrastructural alterations in BDM. In contrast with a striking difference in the production of macrophage-tropic and T-lymphotropic viruses, no significant differences were found in the proportion of macrophages containing retrotranscribed genomes of HIV1-. HIV1 DNA was detected by in situ hybridization in 93, 100, and 80% of macrophages infected with HIV1-PAR, HIV1-LAV, and HIV1-NDK, respectively. A higher level of HIV1 DNA was detected by polymerase chain reaction in the BDM infected with HIV1-PAR than in that infected with HIV1-LAV and HIV1-NDK. The results indicate that both macrophage-tropic as well as T-lymphotropic viruses can enter and retrotranscribe their genomes in a vast majority of macrophages.
Insights
Macrophage-tropic HIV1-PAR and T-lymphotropic HIV1 strains can infect blood-derived macrophages (BDM). While HIV1-PAR efficiently produces virus, both types of HIV1 can integrate their genetic material into macrophages.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) exhibits tropism for both macrophages and T-lymphocytes.
- Understanding differential viral replication and genome integration in macrophages is crucial for HIV-1 pathogenesis.
Purpose of the Study:
- To compare the infectivity and replication of a macrophage-tropic HIV-1 strain (HIV1-PAR) with T-lymphotropic strains (HIV1-LAV, HIV1-NDK) in blood-derived macrophages (BDM).
- To investigate the extent of viral RNA and DNA presence in macrophages after infection with different HIV-1 strains.
Main Methods:
- Isolation of HIV1-PAR from cerebrospinal fluid.
- Infection of BDM with HIV1-PAR, HIV1-LAV, and HIV1-NDK.
- Detection of viral RNA and DNA using in situ hybridization and polymerase chain reaction (PCR).
- Assessment of cytopathic effects and viral production (p24gag).
Main Results:
- HIV1-PAR induced varying levels of viral production in BDM, with detectable RNA in 15-66% of cells.
- T-lymphotropic strains HIV1-LAV and HIV1-NDK showed low viral production and minimal RNA expression in BDM.
- Ultrastructural alterations were observed only with HIV1-NDK.
- Despite differences in viral production, a high proportion of macrophages contained retrotranscribed HIV-1 DNA (80-100%) across all strains.
- Higher levels of integrated HIV-1 DNA were found in BDM infected with HIV1-PAR compared to T-lymphotropic strains.
Conclusions:
- Both macrophage-tropic and T-lymphotropic HIV-1 strains can successfully enter and initiate reverse transcription in a majority of macrophages.
- Differential viral production in macrophages may depend on the specific HIV-1 strain's tropism.
- Macrophages serve as a significant reservoir for HIV-1, regardless of the infecting viral strain's primary tropism.