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Published on: November 23, 2016
Use of chemokine receptors by poxviruses
A S Lalani1, J Masters, W Zeng
1The John P. Robarts Research Institute and Department of Immunology, The University of Western Ontario, London, Ontario N6G 2V4, Canada.
Abstract:
Chemokine receptors serve as portals of entry for certain intracellular pathogens, most notably human immunodeficiency virus (HIV). Myxoma virus is a member of the poxvirus family that induces a lethal systemic disease in rabbits, but no poxvirus receptor has ever been defined. Rodent fibroblasts (3T3) that cannot be infected with myxoma virus could be made fully permissive for myxoma virus infection by expression of any one of several human chemokine receptors, including CCR1, CCR5, and CXCR4. Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin. These findings suggest that poxviruses, like HIV, are able to use chemokine receptors to infect specific cell subtypes, notably migratory leukocytes, but that their mechanisms of receptor interactions are distinct.
Insights
Myxoma virus, a poxvirus, uses chemokine receptors like CCR5 for cell entry, similar to HIV. However, its infection mechanism differs, offering new insights into viral tropism and host-pathogen interactions.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Chemokine receptors are known entry points for intracellular pathogens like HIV.
- The receptor for myxoma virus, a poxvirus causing disease in rabbits, has not been identified.
Purpose of the Study:
- To investigate whether chemokine receptors mediate myxoma virus entry into cells.
- To compare the viral entry mechanisms of poxviruses and HIV.
Main Methods:
- Transfection of rodent fibroblasts (3T3) with human chemokine receptors (CCR1, CCR5, CXCR4).
- Assessing myxoma virus infectivity in engineered 3T3 cells.
- Inhibiting infection using specific receptor antagonists and antibodies.
Main Results:
- Expression of CCR1, CCR5, or CXCR4 rendered 3T3 cells permissive to myxoma virus infection.
- Myxoma virus infection of 3T3-CCR5 cells was inhibited by RANTES and anti-CCR5 antibodies.
- Inhibitors blocking HIV-1 entry did not affect myxoma virus infection.
Conclusions:
- Poxviruses, like HIV, can utilize chemokine receptors for cell entry.
- Myxoma virus employs distinct receptor interaction mechanisms compared to HIV.
- Chemokine receptors may facilitate poxvirus infection of specific cell types, such as migratory leukocytes.
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