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Simian immunodeficiency viruses from multiple lineages infect human macrophages: implications for cross-species
Tobias A Grimm1, Brigitte E Beer, Vanessa M Hirsch
1Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Theraputics Research and Review, Center for Bioligics Evaluations and Review, US Food and Drugs Administration, National Institutes of Health , Rockville, Maryland 20852, USA.
Abstract:
Zoonotic transfer of simian immunodeficiency virus (SIV) from chimpanzees and sooty mangabeys to humans has been documented on at least seven occasions. Several recently identified SIV isolates have also been shown to replicate efficiently in human peripheral blood mononuclear cells (PBMCs) in vitro, indicative of the potential for additional cross-species transmission via T cell infection. Although SIV predominantly uses the macrophage-tropic HIV chemokine coreceptor CCR5, little is known about the ability of SIV to infect human macrophages. In this study, 16 SIV isolates belonging to five different primate lentivirus lineages were tested for their ability to infect human monocyte-derived macrophages (MDMs). Twelve of the viruses were capable of infecting MDMs, and 11 of these were also able to replicate in human PBMCs. The replication capacity of the isolates differed within and between the various families and was dependent on particular donor macrophages. Our results suggest that most simian lentiviruses characterized to date not only have the ability to infect primary human T lymphocytes but also replicate efficiently in macrophages, thereby increasing the potential for cross-species transmission into the human population. Comparative studies using these isolates may facilitate the identification of characteristics that contribute to virus infectivity and pathogenicity.
Insights
Most simian lentiviruses can infect human T cells and macrophages, increasing zoonotic disease risk. Understanding these simian immunodeficiency virus (SIV) characteristics is crucial for preventing cross-species transmission to humans.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Zoonotic transfer of simian immunodeficiency virus (SIV) from primates to humans has occurred multiple times.
- SIV's ability to infect human peripheral blood mononuclear cells (PBMCs) suggests potential for cross-species transmission.
- Limited knowledge exists regarding SIV's capacity to infect human macrophages, despite SIV's use of the CCR5 coreceptor.
Purpose of the Study:
- To investigate the infectivity of various SIV isolates in human monocyte-derived macrophages (MDMs).
- To assess the replication efficiency of SIV isolates in both human MDMs and PBMCs.
- To identify characteristics of SIV that may contribute to cross-species transmission and pathogenicity.
Main Methods:
- Testing of 16 SIV isolates from five primate lentivirus lineages for infectivity in human MDMs.
- Evaluation of viral replication in human PBMCs for isolates that infected MDMs.
- Analysis of replication capacity variations among isolates and dependence on donor macrophage characteristics.
Main Results:
- Twelve of the 16 tested SIV isolates successfully infected human MDMs.
- Eleven of the MDM-infecting isolates also demonstrated efficient replication in human PBMCs.
- Significant differences in replication capacity were observed between SIV families and donor macrophages.
Conclusions:
- Most characterized simian lentiviruses can infect primary human T lymphocytes and replicate in macrophages.
- These findings highlight an increased potential for cross-species transmission of SIV to the human population.
- Further comparative studies are essential for identifying viral factors influencing infectivity and pathogenicity.