The major histocompatibility complex of chickens controls the infection of early chicken embryos by MC29 virus
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Published on: July 29, 2012
I Hlozanek1, C Corbel, F Dieterlen-Lièvre
1Institut d'Embryologie Cellulaire et Moléculaire du C.N.R.S., Nogent sur Marne, France.
Abstract:
Embryos from isogeneic chicken lines belonging to different haplotypes and known to be resistant to infection by avian retroviruses of subgroups A and E were infected on the 3rd (E3) and 5th day (E5) of incubation with MC29 virus (MC29-RAV-1 pseudotype; A subgroup-derived envelope). Despite the trait for resistance, E3 embryos developed the specific heart tumors previously described in outbred E3 embryos. The CB line (B12/B12, C/AE) was more susceptible than the congenic line CC (B4/B4, C/AE). In both lines, the heart was the unique target at E3 for MC29. No tumors of the heart or other organs appeared upon infection at E5 or E10. In the A subgroup susceptible line 6 (B2/B2, C/E) both heart (50%) and skin (100%) were transformed upon E3 infection. Hybrids of line 6 with the CB line expressed skin (100%) and heart (95.4%) tumors. On the other hand, the 6 x CC combination revealed 96.7% of skin tumors while heart tumors occurred only in 1 of 31 embryos (3.2%). To distinguish the respective influences of the MHC and of the tv-a allele, crosses with the la line (B7/B7, C/O) were carried out and tested with MC29. The findings indicate that resistance of the embryos to MC29 heart tumors is associated with the B4/B4 haplotype, supporting the interpretation that the MHC has a role in MC29 cell tropism and v-myc expression. The target cells in tumors were determined by immunofluorescence staining. Cells infected in the heart belonged to the myogenic lineage, as expected from previous studies. In skin anomalies the epidermal cells were double-stained with anticytokeratin and anti-env antibodies, many cells in the dermis also reacted with anti env antibodies.
Insights
Chicken embryos infected with MC29 virus developed heart tumors, with resistance linked to the B4/B4 major histocompatibility complex (MHC) haplotype. This suggests MHC influences avian retrovirus tropism and oncogene expression.
Area of Science:
- Virology
- Oncology
- Immunogenetics
Background:
- Avian retroviruses, like MC29, can cause tumors in chickens.
- Chicken lines with specific major histocompatibility complex (MHC) haplotypes exhibit varying resistance to viral infections.
Purpose of the Study:
- To investigate the role of MHC haplotypes in susceptibility to MC29 virus-induced heart tumors.
- To determine the cellular targets of MC29 virus in different chicken lines and infection timings.
Main Methods:
- Infection of isogeneic chicken embryos from different lines with MC29 virus at various incubation stages (E3, E5, E10).
- Tumor incidence assessment in heart and skin tissues.
- Cross-breeding experiments to analyze genetic influences (MHC and tv-a allele).
- Immunofluorescence staining to identify infected cell lineages (myogenic, epidermal, dermal).
Main Results:
- Early (E3) MC29 infection induced heart tumors in susceptible chicken lines, with varying susceptibility observed between CB (B12/B12) and CC (B4/B4) lines.
- Resistance to heart tumors was associated with the B4/B4 MHC haplotype.
- Later infection (E5, E10) did not result in tumor formation.
- Skin tumors were prevalent in susceptible lines and hybrids, with different MHC backgrounds influencing tumor type.
- Infected heart cells were of myogenic lineage; skin anomalies involved epidermal and dermal cells.
Conclusions:
- The major histocompatibility complex (MHC) plays a significant role in determining resistance to MC29 virus-induced heart tumors in chicken embryos.
- MHC haplotype influences MC29 virus tropism and potentially v-myc oncogene expression.
- Cellular targets differ between heart (myogenic) and skin (epidermal/dermal) tumors, indicating distinct cellular tropisms.
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