Influence of CCL2-mediated modulation of ALIX in the budding and replication of viruses from multiple families

C-C motif ligand 2 (CCL2) plays a regulatory role in the budding and release of HIV-1 in macrophages and HeLa cells. CCL2 signaling mobilizes ALG-2-interacting protein X (ALIX) from the F-actin cytoskeleton to the soluble cytosol, where it is accessible for recruitment by the HIV-1 Gag polyprotein in the assembling virions at the plasma membrane. In previous studies, CCL2 immunodepletion, which blocks CCL2 signaling, resulted in ALIX sequestration to the F-actin cytoskeleton and inhibited virus production. Here, we developed a HeLa CCL2 gene knockout cell line and found that abrogation of CCL2 signaling can be restored by CCL2 addition, as evidenced by the restoration of ALIX to the cytosolic fraction and rescue of HIV-1 release. Employing such a system, we tested Simian Immunodeficiency Virus, Equine Infectious Anemia Virus, Herpes Simplex Virus type 1, Dengue, and Hazara virus for their dependence on ALIX for virus replication. The results indicate that CCL2 signaling and ALIX release from F-actin may play a role in the replication of several viruses.

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Publication Details

Journal
mBio
Published
2025-09-25
DOI
https://doi.org/10.1128/mbio.02241-25
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Influence of CCL2-mediated modulation of ALIX in the budding and replication of viruses from multiple families

John McCullough, Jacob Berrigan, Duncan W. Wilson, Jinghang Zhang et al.
mBio
HIV Research and Treatment
article

Influence of CCL2-mediated modulation of ALIX in the budding and replication of viruses from multiple families

John McCullough, Jacob Berrigan, Duncan W. Wilson, Jinghang Zhang, Pratyush Kumar Das, Swati Haldar, Anne R. Bresnick, Dina Mofed, Vinayaka R. Prasad, David Ajasin, Anjali Gowripalan, Margaret Kielian, Ganjam V. Kalpana, Kartik Chandran, Yongwei Zhang, Nivedita Pujari
article en

Abstract

C-C motif ligand 2 (CCL2) plays a regulatory role in the budding and release of HIV-1 in macrophages and HeLa cells. CCL2 signaling mobilizes ALG-2-interacting protein X (ALIX) from the F-actin cytoskeleton to the soluble cytosol, where it is accessible for recruitment by the HIV-1 Gag polyprotein in the assembling virions at the plasma membrane. In previous studies, CCL2 immunodepletion, which blocks CCL2 signaling, resulted in ALIX sequestration to the F-actin cytoskeleton and inhibited virus production. Here, we developed a HeLa CCL2 gene knockout cell line and found that abrogation of CCL2 signaling can be restored by CCL2 addition, as evidenced by the restoration of ALIX to the cytosolic fraction and rescue of HIV-1 release. Employing such a system, we tested Simian Immunodeficiency Virus, Equine Infectious Anemia Virus, Herpes Simplex Virus type 1, Dengue, and Hazara virus for their dependence on ALIX for virus replication. The results indicate that CCL2 signaling and ALIX release from F-actin may play a role in the replication of several viruses.

mBioVol. 16(11)
Albert Einstein College of Medicine (US), University of Utah (US)
City University of New York, National Institutes of Health, Center for AIDS Research, University of Washington, National Cancer Institute
Openalex Percentile: Top 72%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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