Endocytosis and a low-pH step are required for productive entry of equine infectious anemia virus.
Abstract: Recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-pH step. The entry mechanism of equine infectious anemia virus (EIAV) has yet to be examined. Here, we demonstrate that wild-type strains of EIAV require a low-pH step for productive entry. Lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of EIAV. The presence of ammonium chloride (30 mM), monensin (30 microM), or bafilomycin A (50 nM) in the medium dramatically decreased the number of EIAV antigen-positive cells. We found that a low-pH step was required for EIAV infection of tissue culture cell lines as well as primary cells, such as endothelial cells and monocyte-derived macrophages. The ammonium chloride treatment did not reduce virion stability, nor did the treatment prevent virion binding to cells. Consistent with a requirement for a low-pH step, virion infectivity was enhanced more than threefold by brief low-pH treatment following binding of viral particles to permissive cells. A superinfecting variant strain of EIAV, vMA-1c, did not require a low-pH step for productive infection of fibroblasts. However, lysosomotropic agents were inhibitory to vMA-1c infection in the other cell types that vMA-1c infected but did not superinfect, indicating that the entry pathway used by vMA-1c for superinfection abrogates the need for the low-pH step.
Publication Date: 2005-11-12 PubMed ID: 16282447PubMed Central: PMC1287591DOI: 10.1128/JVI.79.23.14482-14488.2005Google Scholar: Lookup
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Summary
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This research explores the entry mechanism of the equine infectious anemia virus (EIAV), demonstrating that a low-pH step is required for effective entry into host cells. The study also observes that the virus’s infectivity can be notably enhanced by a brief low-pH treatment following binding to permissive cells.
Understanding the Entry Mechanism of EIAV
- The paper centers on the penetration process of the EIAV and how it effectively enters cells. Previous evidence revealed that the penetration of some retroviruses into cells depends on a vesicle-localized, low-pH stage, and this study hypothesizes that the same mechanism applies to EIAV.
- The research demonstrates that a reduction in pH is required for productivity and that interfering with internal vesicle acidification could inhibit EIAV productivity. Various lysosomotropic agents such as ammonium chloride, monensin, and bafilomycin A have been used to achieve this effect.
- Interestingly, the study found that briefly subjecting the virus to low-pH conditions significantly boosted its infectivity after it binds to the cells.
Insights into EIAV Infection of Tissue Culture Cell Lines
- Furthermore, it was observed that the low-pH step is necessary not only for wild-type strains of EIAV but also in the infection of tissue culture cell lines and primary cells, including endothelial cells and monocyte-derived macrophages.
- On the other hand, the EIAV variant strain dubbed vMA-1c seems to utilize a different entry pathway, one that obviates the need for the low-pH step when infecting fibroblasts. However, vMA-1c infection was still sensitive to the inhibitory action of lysosomotropic agents in cell types that it infected but were incapable of superinfection.
Significance and Implications of Findings
- The research underscores the significance of the low-PH stage in reproducing EIAV in host cells. Interfering with this stage appears to significantly impede the virus’s activity, opening up potential therapeutic applications for these insights.
- These findings also shed light on differences in the entry pathways used by various strains or forms of EIAV, which could have implications for the development of treatments targeting specific strains or forms of the virus.
Cite This Article
APA
Brindley MA, Maury W.
(2005).
Endocytosis and a low-pH step are required for productive entry of equine infectious anemia virus.
J Virol, 79(23), 14482-14488.
https://doi.org/10.1128/JVI.79.23.14482-14488.2005 Publication
Researcher Affiliations
- Dept. Microbiology, University of Iowa, Iowa City, IA 52242, USA.
MeSH Terms
- Ammonium Chloride / pharmacology
- Animals
- Endocytosis / drug effects
- Endocytosis / physiology
- Equine Infectious Anemia / etiology
- Equine Infectious Anemia / virology
- Horses
- Hydrogen-Ion Concentration
- Infectious Anemia Virus, Equine / drug effects
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / pathogenicity
- Infectious Anemia Virus, Equine / physiology
- Virion / physiology
Grant Funding
- T32 AI007533 / NIAID NIH HHS
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