Evolution of broad host range in retroviruses leads to cell death mediated by highly cytopathic variants - PubMed (original) (raw)
Evolution of broad host range in retroviruses leads to cell death mediated by highly cytopathic variants
G Jonah A Rainey et al. J Virol. 2006 Jan.
Abstract
The ability of many retroviruses to cause disease can be correlated to their cytopathic effect (CPE) in tissue culture characterized by an acute period of cell death and viral DNA accumulation. Here, we show that mutants of a subgroup B avian retrovirus (Alpharetrovirus) cause a very dramatic CPE in certain susceptible avian cells that is coincident with elevated levels of apoptosis, as measured by nuclear morphology, and persistent viral DNA accumulation. These mutants also have a broadly extended host range that includes rodent, cat, dog, monkey, and human cells (31). Previously, we have shown that the mutants exhibit diminished resistance to superinfection. The results presented here have important implications for the process of evolution of retroviruses to use distinct cellular receptors.
Figures
FIG. 1.
Viral replication and cell growth. Cells were infected and passaged at equal density every 3 to 4 days. RT activity was measured and plotted to give viral growth curves for the DF1 cell line (A) and a CEF cell strain (B). The average of three viable cell counts was used to determine the relative increase in cell number for the DF1 cells (C) and CEF cells (D). Results are the average of three replicates (± standard error of the mean [SEM]) from a single experiment, representative of three independent experiments. The interval during which the strongest CPE was evident for DF1 cells infected with L154S and LT154/155SI is indicated (A and C).
FIG. 2.
Micrographs of infected cells. Cells were examined using phase-contrast microscopy and photographed with a charge-coupled device camera. Typical fields are shown for cells infected with each virus for DF1 (16 days) and CEF (14 days) cells. Black bars, 100 μm.
FIG. 3.
Apoptosis in infected cultures. Adherent and nonadherent cells were pooled and stained with Hoechst 33342 dye. Apoptotic nuclei were scored as a percentage of total nuclei by fluorescence microscopy. (A) DF1 cell line. The interval with the strongest CPE is indicated. (B) CEF cell strain. Results are the average of three counts (± SEM) from a single experiment, representative of two independent experiments. The area under the curve was determined to indicate cumulative apoptosis levels (arbitrary units) in infected cells and plotted versus time for DF1 (C) and CEF (D) cells.
FIG. 4.
Accumulation of viral DNA. Southern blots of total cellular DNA were hybridized to a labeled gag probe. Data from DF1 cells infected with PrB and L154S are shown (A), and these as well as the others were quantitated with a phosphorimager and plotted (B to E). Integrated high-molecular-weight (C and E) and unintegrated (B and D) DNA forms were measured for DF1 (B and C) and CEF (D and E) cells, and the DNA copy number was obtained by comparison to a standard curve present on every gel. Results are presented from a single experiment, representative of two independent experiments.
FIG. 5.
Induction of apoptosis by cycloheximide in chronically infected DF1 cells. Chronically infected cells (60 days postinfection) were treated with cycloheximide (10 μg/ml), harvested at indicated times, and scored for apoptosis as described in the legend to Fig. 3. Results are the average of three replicates (± SEM) from a single experiment, representative of three independent experiments.
Similar articles
- A single-amino-acid substitution in the TvbS1 receptor results in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroups B and D and resistance to infection by subgroup E in vitro and in vivo.
Reinisová M, Senigl F, Yin X, Plachy J, Geryk J, Elleder D, Svoboda J, Federspiel MJ, Hejnar J. Reinisová M, et al. J Virol. 2008 Mar;82(5):2097-105. doi: 10.1128/JVI.02206-07. Epub 2007 Dec 19. J Virol. 2008. PMID: 18094190 Free PMC article. - Variation in avian retrovirus genomes.
Coffin JM, Tsichlis PN, Barker CS, Voynow S, Robinson HL. Coffin JM, et al. Ann N Y Acad Sci. 1980;354:410-25. doi: 10.1111/j.1749-6632.1980.tb27982.x. Ann N Y Acad Sci. 1980. PMID: 6261656 No abstract available. - [Retroviruses with 2 oncogenes].
Rupniewska ZM. Rupniewska ZM. Postepy Hig Med Dosw. 1989;43(1):29-52. Postepy Hig Med Dosw. 1989. PMID: 2560832 Review. Polish. - Cytocidal effect caused by the envelope glycoprotein of a newly isolated avian hemangioma-inducing retrovirus.
Resnick-Roguel N, Burstein H, Hamburger J, Panet A, Eldor A, Vlodavsky I, Kotler M. Resnick-Roguel N, et al. J Virol. 1989 Oct;63(10):4325-30. doi: 10.1128/JVI.63.10.4325-4330.1989. J Virol. 1989. PMID: 2550668 Free PMC article.
Cited by
- Rapid adaptive evolution of avian leukosis virus subgroup J in response to biotechnologically induced host resistance.
Matoušková M, Plachý J, Kučerová D, Pecnová Ľ, Reinišová M, Geryk J, Karafiát V, Hron T, Hejnar J. Matoušková M, et al. PLoS Pathog. 2024 Aug 15;20(8):e1012468. doi: 10.1371/journal.ppat.1012468. eCollection 2024 Aug. PLoS Pathog. 2024. PMID: 39146367 Free PMC article. - Unique Structure and Distinctive Properties of the Ancient and Ubiquitous Gamma-Type Envelope Glycoprotein.
Hogan V, Johnson WE. Hogan V, et al. Viruses. 2023 Jan 18;15(2):274. doi: 10.3390/v15020274. Viruses. 2023. PMID: 36851488 Free PMC article. Review. - Avian Sarcoma and Leukosis Virus Envelope Glycoproteins Evolve to Broaden Receptor Usage Under Pressure from Entry Competitors †.
Munguia A, Federspiel MJ. Munguia A, et al. Viruses. 2019 Jun 5;11(6):519. doi: 10.3390/v11060519. Viruses. 2019. PMID: 31195660 Free PMC article. - Reverse Engineering Provides Insights on the Evolution of Subgroups A to E Avian Sarcoma and Leukosis Virus Receptor Specificity.
Federspiel MJ. Federspiel MJ. Viruses. 2019 May 30;11(6):497. doi: 10.3390/v11060497. Viruses. 2019. PMID: 31151254 Free PMC article. Review.
References
- Bernstein, C., H. Bernstein, C. M. Payne, and H. Garewal. 2002. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res. 511:145-178. - PubMed
- Boeke, J. D., and J. P. Stoye. 1997. Retrotransposons, endogenous retroviruses, and the evolution of retroelements, p. 343-435. In J. M. Coffin, S. H. Hughes, and H. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory Press, Plainview, N.Y. - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous