Avian leucosis, Marek's & other diseases

Posted by: Wieslaw

Avian leucosis, Marek's & other diseases - 02/27/11 01:25 PM

Here is the information about connection between slow feathering gene and avian leucosis I've promised before.


Recently, the endogenous viral gene ev21 has been shown to be closely linked to the sex-linked dominant slowfeathering gene (K) that is used to feather-sex a large proportion of commercial white-egg-producing chickens (3,20). ev21 has been shown to code for the complete endogenous virus EV21.

If this subgroup E endogenous virus is congenitally transmitted to fast-feathering female progeny that lack gene ev21, these birds could have a reduced immune response to exogenous virus infection. Such a mechanism could lead to the increased ALV infection rate and poor performance observed in fast-feathering female progeny of slow-feathering dams (15).

Certain live poultry vaccines are highly effective when administered on day 18 or 19 of incubation (19). Contamination of these vaccines with infectious endogenous viruses could limit the immune response of vaccinated chickens to exogenous ALV infection. However, a detrimental effect would be expected only if the embryos were susceptible to subgroup E ALV infection and if infection of embryos on day 18 or 19 of incubation rather than on day 6 indeed limits immune response to exogenous ALV.
Since endogenous-virus-induced limitation of immune response
to ALV is clearly specific for that class of viruses (6; Crittenden, unpublished data), the detrimental effects of endogenous-virus expression would not adversely influence chicken flocks that were free of exogenous ALV infection.

It is from here:


Other quotes will follow, but this one has been the easiest to comprehend (by me smile )
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 03/04/11 05:57 AM

Here is another abstract.It is taken from here:


The difference is in the supposition that the viral insertion in White Leghorns may have happened in the k+ itself.

Poult Sci. 1988 Feb;67(2):191-7.

Association of the slow feathering (K) and an endogenous viral (ev21) gene on the Z chromosome of chickens.
Bacon LD, Smith E, Crittenden LB, Havenstein GB.

US Department of Agriculture, Agricultural Research Service, East Lansing, Michigan 48823.

A dominant sex-linked gene, K, regulates slow feathering (SF), whereas a recessive allele, k+, determines rapid feathering (RF) in chickens. This trait provides a convenient and inexpensive approach to gender identification of White Leghorn (WL) chicks at hatch, i.e., in a sex-linked mating using k+/k+ males mated with K/- females, the K/k+ male chicks are SF, and the k+/- females are RF. However, in many WL strains, female progeny of SF dams produce fewer eggs and have higher mortality than progeny of RF dams. This loss in productivity has been attributed to higher infection and shedding rates for leukosis viruses (ALV) in SF than in RF dam lines. Because infectious endogenous viruses (EV) can induce immunological tolerance to ALV, we examined the expression and distribution of ev genes in SF and RF siblings from heterozygous K/k+ sires and k+/- dams. Infectious ALV and EV were detected by cocultivation of frozen heparinized blood cells on selected chick embryo fibroblasts and culture supernatants were tested for viral antigen by enzyme-linked immunosorbent assay tests. Specific ev genes were identified as restriction fragment length polymorphisms after hybridization with a recombinant plasmid containing the complete genome of a Rous-associated virus. It was concluded that ev21 and K genes are tightly linked because, in different WL crosses, all SF chicks inherited ev21 but RF siblings uniformly lacked ev21. Alternatively, the K gene in WL may be a mutation resulting from the insertion of ev21 in the k+ gene. The SF chicks which harbor ev21 expressed infectious EV21; evidence that EV21 may influence susceptibility to ALV is presented.

I'm not sure I understand this line:
"This loss in productivity has been attributed to higher infection and shedding rates for leukosis viruses (ALV) in SF than in RF dam lines".

Should it be understood that the SF birds themselves are more succeptible to AVL infection as well?
Posted by: Sigi

Re: Avian leucosis, Marek's & other diseases - 03/05/11 06:03 PM

Yes, my experience. Slow deaths in slow feathering birds, lethargic and most around 5-6 months in my case. They just wasted away, it was not 'leukosis' but another viral blood cancer is what the vet suspected afther the 6th case in one line of slow feathering Serama. I never bred the cockerels anyway, but I remembered their father was very slow in feathering, also in mature feathers, at 6 months he still didn't developed a full tail with the 2 main sickles, actually his tail was always short.
Not all of his children died. But I culled them all, remembering the ALV21 story which was horror in poultry industry late 90s.
David knows more about this. It was discussed on an international poultry congress.
Posted by: KazJaps

Re: Avian leucosis, Marek's & other diseases - 03/06/11 08:40 AM

Both R.Okimoto and D.Caveny have discussed the issue of K locus and ALV in the past (if you want to do a search). From memory, I think it might be discussed in "Poultry Breeding & Genetics" also. On a side note, R.Okimoto mentioned that the K mutation reverts back to wild type at a high rate (another reason why not so good for large scale commercial use for sexing day-olds)

The following suggests that it is the close linkage between K and ev21 loci giving the correlations of late-feathering / poor ALV resistance, ie hasn't been determined that K mutation alone gives the poor ALV resistance (ie possibly the ev21 allele mutation alone):

Although the LF phenotype facilitates the sexing of chicks, the K allele is also associated with a reduction in egg production, an increase in infection by lymphoid leucosis virus [7], and an increase in the mortality rate [8]. These negative side effects may be caused by the presence of the endogenous retrovirus 21 (ev21) [8]. Concordance between expression of ev21 and the LF phenotype indicated a linkage of less than 0.3 cM between K and the ev21 locus [9,10]. The ev21 locus consists of an integration site that can be occupied (ev21+) or unoccupied (ev21-). EF animals were found to have only one unoccupied site per Z chromosome; whereas, LF animals have at least one Z chromosome with an unoccupied and an occupied site [11]. A study on the organization of the K allele concluded the integration of ev21 into one of two large homologous segments located on the Z chromosome of LF chickens [12]. EF revertants carrying an occupied site have been observed; therefore, it was concluded that ev21 itself could not be the sole cause of the LF phenotype [13].

.......Although the LF phenotype facilitates the sexing of chicks at hatching, expression of ev21 is associated with the negative side effects of the K allele [7,8]. The establishment of a line where late-feathering is not associated with decreased egg production and tolerance to exogenous avian leucosis virus infection would be of prime commercial interest. Obviously, the search for the K allele lacking the occupied site is an effective approach. This search for revertants and the establishment of a line can be done by combining the TaqMan K test and the ev21 test proposed by Tixier-Boichard [15].

* so it has been determined that ev21 doesn't give the K - late feathering phenotype.

Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken.
Elferink MG, Vallée AA, Jungerius AP, Crooijmans RP, Groenen MA.
BMC Genomics. 2008 Aug 20;9:391.
full paper
*As the paper title indicates, they have narrowed down the K locus gene to two candidates: PRLR & SPEF2 genes.

The following was an interesting study on a strain of very late feathering chickens from Indonesia:

A deleted retroviral insertion at the ev21-K complex locus in Indonesian chickens.
Tixier-Boichard M, Boulliou-Robic A, Morisson M, Coquerelle G, Horst P, Benkel B.
Poult Sci. 1997 May;76(5):733-42.
full paper
*this phenotype (& genotype) more complex.
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 03/08/11 05:54 AM

Kazjaps, WOW!, that is a nice piece of information , thanks.
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 03/12/11 06:14 PM

Originally Posted By: Kazjaps
On a side note, R.Okimoto mentioned that the K mutation reverts back to wild type at a high rate (another reason why not so good for large scale commercial use for sexing day-olds)

Originally Posted By: R.Okimoto
Some mutations are very frequent and happen all the time. The sex-linked late-feathering locus in chickens mutates back to wild-type early feathering at a rate of 1 in a thousand. Commercial late-feathering lines developed for feather sexing have to be constantly screened for early feathering revertants.

It is in this thread .

While we are at slow feathering: the gene has the tendency to mutate back. But what about the other way around? Do the rapid feathering mutate to slow feathering with increased frequency(compared to other genes)? Any known reports?
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/13/13 01:32 PM

I have not forgotten this thread, I just have been too busy to update it. In the meantime , I have found some articles you need to read.


and this
Posted by: Marina

Re: Avian leucosis, Marek's & other diseases - 01/13/13 02:11 PM

Wieslaw - thanks for the links. Very interesting.

Is there a way I can read the whole article, not just the abstract?
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/13/13 02:51 PM

Usually there is a place you can read the whole article if you follow some links, but you have to pay for the access.
Posted by: jonnydot

Re: Avian leucosis, Marek's & other diseases - 01/13/13 07:42 PM

I "think" this is related and I have some questions ..http://www.ncbi.nlm.nih.gov/pubmed/16457736BMC Genomics. 2006 Feb 5;7:19.
Complete association between a retroviral insertion in the tyrosinase gene and the recessive white mutation in chickens.
Chang CM, Coville JL, Coquerelle G, Gourichon D, Oulmouden A, Tixier-Boichard M.

UMR Génétique et Diversité Animales, INRA/INA P-G, Centre de Recherches de Jouy, 78352 Jouy-en-Josas, France. chang@dga2.jouy.inra.fr

In chickens, three mutant alleles have been reported at the C locus, including the albino mutation, and the recessive white mutation, which is characterized by white plumage and pigmented eyes. The albino mutation was found to be a 6 bp deletion in the tyrosinase (TYR) gene. The present work describes an approach to identify the structural rearrangement in the TYR gene associated with the recessive white mutation.

Molecular analysis of the chicken TYR gene has revealed a major structural difference (Restriction Fragment Length Polymorphism, RFLP) in the genomic DNA of the recessive white chicken. A major size difference of 7.7 kb was found in intron 4 of the TYR gene by long-range PCR. Molecular cloning and sequencing results showed the insertion of a complete avian retroviral sequence of the Avian Leukosis Virus (ALV) family. Several aberrant transcripts of the tyrosinase gene were found in 10 week old recessive white chickens but not in the homozygous wild type colored chicken. We established a rapid genotyping diagnostic test based on the discovery of this retroviral insertion. It shows that all homozygous carriers of this insertion had a white plumage in various chicken strains. Furthermore, it was possible to distinguish heterozygous carriers from homozygous normal chickens in a segregating line.

In this study, we conclude that the insertion of a complete avian retroviral sequence in intron 4 of the tyrosinase gene is diagnostic of the recessive white mutation in chickens. This insertion causes aberrant transcripts lacking exon 5, and we propose that this insertion is the causal mutation for the recessive white allele in the chicken.

[PubMed - indexed for MEDLINE]

Free PMC Article

Images from this publication.See all images (11) Free text
Figure 1
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Figure 11
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Publication Types, MeSH Terms, Substances
LinkOut - more resources ...........My questions are ...does this mean that this virus is still active ? or has it just changed dna ,and if it is active would it mean that in those c/c birds that leak straw the virus is not as prolific as in those that are a clean white and does it mean that if a leaky bird was over a clean white bird that the offspring would get a stronger dose of the virus ? sorry if I have asked in the wrong place
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/14/13 03:37 PM

You have asked the correct place, but it is not sure you will get an answer right now. I think people who keep recessive whites should be asked to express their opinion on general health and longevity of the birds, whether they observed something 'suspect'compared to other birds.
Posted by: ssc

Re: Avian leucosis, Marek's & other diseases - 01/15/13 04:27 AM

Could some strains of Copper Black Marans carry recessive white?
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/15/13 04:25 PM

Originally Posted By: ssc
Could some strains of Copper Black Marans carry recessive white?

Why not? There are recessive white Marans.

Here is another horror, this time with Marek's

Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 02/01/13 05:05 PM

Some more links:

Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 04/24/13 03:47 PM

I have found an easy to understand abstract.


Institute for Animal Health, Compton, Newbury, Berks, RG20 7NN, United Kingdom


Three species of avian retrovirus cause disease in poultry: the avian leukosis/sarcoma virus
(ALSV), reticuloendotheliosis virus (REV), and lymphoproliferative disease virus (LPDV) of turkeys. The
ALSV can be classified as slowly transforming viruses, which lack a viral oncogene, and acutely transforming
viruses, which possess a viral oncogene. Slowly transforming viruses induce late onset leukoses of the B cell
lymphoid, erythroid, and myeloid cell lineages, and other tumors, by viral promoter insertion into the
genome of a host cell and activation of a cellular protooncogene. The various acutely transforming leukemia and sarcoma viruses induce leukotic or other tumors rapidly and carry one or another (sometimes two) viral oncogenes, of which some 15 have been identified. The ALSV fall into six envelope subgroups, A through E, and the recently recognized J subgroup, which induces myeloid leukosis. With the exception of Subgroup E viruses, these viruses spread vertically and horizontally as infectious virions, and are termed exogenous viruses. Subgroup E viruses are usually spread genetically as DNA proviruses (often defective) in host germ cell genome, and are termed endogenous viruses. Several other families of endogenous viruses also exist, one of which, endogenous avian retrovirus (EAV), is related to Subgroup J ALV. Exogenous viruses, and sometimes endogenous viruses, can have detrimental effects on commercially important production traits. Exogenous viruses are currently controlled by virus eradication schemes. Reticuloendotheliosis virus, which lacks a viral oncogene, causes chronic B cell and T-cell lymphomas in chickens, and also chronic lymphomas in turkeys and other species of birds. An acutely transforming variant of REV, Strain T, carries a viral oncogene, and induces reticuloendotheliosis within a few days. In chickens and turkeys, REV spreads vertically and horizontally. No commercial control schemes are operated. In turkeys, LPDV infection has occurred in several countries, where it caused a lymphoproliferative disease of uncertain nature

It is from here:

Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/24/14 05:11 AM

A propos recessive white viral insertion: I have read, that it is inserted "backwards"(provided I understood correctly), thus should not make a bird more succeptible to avian leucosis(?)

Here is another interesting link


Male-mediated venereal transmission of endogenous avian leukosis virus.
Smith EJ, Fadly AM.
Author information USDA, Agricultural Research Service, Avian Disease and Oncology Laboratory, East Lansing, Michigan 48823.


Congenital transmission of avian leukosis viruses (ALV) occurs readily through the egg, but transmission of ALV through male seminal fluid is considered to be nonexistent or rare. Progeny from mating endogenous late-feathering (LF), K/k+ males carrying an endogenous virus gene (ev21) with virgin early-feathering (EF) k+/w females were examined for the presence of infectious endogenous virus EV21 using an enzyme-labeled immunoassay for viral capsid antigen p27. All 177 LF chicks expressed EV21, p27, and 171 of 175 EF chicks did not express p27. Blood from the four p27-positive EF chicks revealed only infectious Subgroup E ALV as determined by subgroup-specific virus assays. Southern blot DNA hybridizations, however, ruled out germline integration of EV21 among the four infected EF progeny. Virus EV21 was not shed in albumens of the dams. Moreover, antibodies against ALV Subgroups A and E were not detected in dams 17 wk after the first insemination. Chicks infected with EV21 were found only in the first two of six hatches. Data suggested direct infection of the embryos from viremic semen rather than congenital infection through infected hens. Direct male transmission of EV21 to progeny may be the basis for persistence of refractory lines noted in some ALV eradication programs. Based on the absence of recombinants among 352 progeny, ev21 and K appear to be less than .3 cM apart.
Posted by: Redcap

Re: Avian leucosis, Marek's & other diseases - 01/30/14 12:39 AM

In the meanwhile it is known, that infection or reinfection can happen in adult chicken
or even in turkeys

Therefore is has been suggest to revaccinate chicken - best results can be reached with homologous vaccines
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 11/09/17 02:57 PM

A new article on avian influenza

Identifying the genetic basis for resistance to avian influenza in commercial egg layer chickens


Two highly pathogenic avian influenza (HPAI) outbreaks have affected commercial egg production flocks in the American continent in recent years; a H7N3 outbreak in Mexico in 2012 that caused 70% to 85% mortality and a H5N2 outbreak in the United States in 2015 with over 99% mortality. Blood samples were obtained from survivors of each outbreak and from age and genetics matched non-affected controls. A total of 485 individuals (survivors and controls) were genotyped with a 600 k single nucleotide polymorphism (SNP) array to detect genomic regions that influenced the outcome of highly pathogenic influenza infection in the two outbreaks. A total of 420458 high quality, segregating SNPs were identified across all samples. Genetic differences between survivors and controls were analyzed using a logistic model, mixed models and a Bayesian variable selection approach. Several genomic regions potentially associated with resistance to HPAI were identified, after performing multidimensional scaling and adjustment for multiple testing. Analysis conducted within each outbreak identified different genomic regions for resistance to the two virus strains. The strongest signals for the Iowa H5N2 survivor samples were detected on chromosomes 1, 7, 9 and 15. Positional candidate genes were mainly coding for plasma membrane proteins with receptor activity and were also involved in immune response. Three regions with the strongest signal for the Mexico H7N3 samples were located on chromosomes 1 and 5. Neuronal cell surface, signal transduction and immune response proteins coding genes were located in the close proximity of these regions.

Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 11/10/17 04:51 PM

Livestock and poultry density and childhood cancer incidence in nine states in the USA.


Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence.

We found positive associations between AML and broiler chicken densities (RRper 10AU/km2 = 1.14, 95% CI = 1.02-1.26). ALL rates increased with densities of hog operations (RRper operation/100km2 = 1.06, 95% CI = 1.02-1.11). PNS cancer rates were inversely associated with layer chicken density (RRper log of AU/km2 = 0.94, 95% CI = 0.89-0.99). No association was found between any cancer type and densities of cattle, equine, or goats
Posted by: Redcap

Re: Avian leucosis, Marek's & other diseases - 11/13/17 11:55 AM

Cross reference to cancer studies:
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 11/29/17 06:40 AM

Here is an exciting article:

GADD45β, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens
Posted by: KazJaps

Re: Avian leucosis, Marek's & other diseases - 12/26/17 08:23 PM

New 2017 Dec. paper on late feathering & ev21:

A Takenouchi, M Toshishige, N Ito, M Tsudzuki; 2017.
Endogenous viral gene ev21 is not responsible for the expression of late feathering in chickens.
Poultry Science, , pex345, https://doi.org/10.3382/ps/pex345
Abstract only
The late-feathering (LF) gene K on the Z chromosome is an important gene in the chicken industry, which is frequently utilized for the feather sexing, a type of autosexing, of neonatal chicks. The K gene is closely associated with the endogenous ev21 gene from an avian leukosis virus and the incomplete duplication (ID) of prolactin receptor (PRLR) and sperm flagellar protein 2 (SPEF2) genes, and ev21 has been used as a molecular marker to detect LF birds. In the present study, a comprehensive survey for the presence or absence of ev21 and ID across 1,994 birds from 52 chicken breeds, three commercial hybrid groups, and the Red Jungle Fowl revealed that almost all LF breeds have both ev21 and ID. However, only one LF breed (Ingie) has only ID and no ev21. Moreover, this study revealed that almost all early (normal)-feathering (EF) breeds lack both ev21 and ID, but only one breed (White Plymouth Rock) included EF birds with ev21 but no ID. Therefore, regarding LF expression, the results indicated that ID is responsible, but ev21 is not required. Henceforth, ID should be used as a molecular marker to detect LF birds instead of ev21. Because ev21 contains the full genome of an avian leukosis virus, there is a risk of disease development in breeds with this gene. Therefore, the Ingie breed, which has no ev21 at the K locus, represents excellent material for the establishment of new LF stocks.

*Note, earlier research had noted that ev21 positive was not responsible for the late feathering trait, this determined with LF lines where individuals mutated back to wild-type k+ (early feathering) but still ev21 positive. Where the above 2017 research differs is in finding a K late feathering breed that is ev21 negative.

Elferink MG, Vallée AA, Jungerius AP, Crooijmans RP, Groenen MA. 2008.
Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken.
BMC Genomics. 2008;9:391. doi:10.1186/1471-2164-9-391


In the following 2016 research paper the authors believed that the SPEF2 gene & not PRLR might be more responsible for the late feathering phenotype (indicated in their gene expression research):

J. Zhao, J. Yao, F. Li, Z. Yang, Z. Sun, L. Qu, K. Wang, Y. Su, A. Zhang, S. A. Montgomery, T. Geng, H. Cui; 2016.
Identification of candidate genes for chicken early- and late-feathering.
Poultry Science, Volume 95, Issue 7, 1 July 2016, Pages 1498–1503, https://doi.org/10.3382/ps/pew131
Previous studies suggest that prolactin receptor (Prlr) is a potential causative gene for chicken early- (EF) and late-feathering (LF) phenotypes. In this study, we evaluated candidate genes for this trait and determined the expression of 3 genes, including Prlr, sperm flagellar protein 2 (Spef2), and their fusion gene, in the skins of one-day-old EF and LF chicks using RT­qPCR. Data indicated that Prlr expression in the skin did not show significant difference between EF and LF chicks, suggesting Prlr may not be a suitable candidate gene. In contrast, Spef2 expression in the skin displayed a significant difference between EF and LF chicks (P < 0.01), suggesting that Spef2 may be a good candidate gene for chicken feathering. Moreover, dPrlr/dSpef2, the fusion gene, was also a good candidate gene as it was expressed only in LF chicks. However, the expression of the fusion gene was much lower than that of Prlr. Additionally, using strand-specific primers, we found that the fusion gene was transcribed in 2 directions (one from dPrlr promoter, another from dSpef2 promoter), which could result in the formation of a double strand RNA. In conclusion, both Spef2 and the fusion gene are good candidate genes for chicken feathering, but Prlr is not.
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/07/18 06:14 AM

Evaluation of genetic resistance to Salmonella Pullorum in three chicken lines.


Resistance to diseases varies considerably among populations of the same species and can be ascribed to both genetic and environmental factors. Salmonella Pullorum (SP) is responsible for significant losses in the poultry industry, especially in developing countries. To better understand SP resistance in chicken populations with different genetic backgrounds, we orally challenged 3 chicken lines with SP-a highly selected commercial breed (Rhode Island Red, RIR), a local Chinese chicken (Beijing You, BY), and a synthetic layer line (dwarf, DW)-at 4 d of age. Two traits related to SP resistance, survival, and bacterial carriage in the spleen were evaluated after infection. Survival rates were recorded up to 40 d of age when all chickens still alive were killed to verify the presence of SP in the spleen to determine carrier state. Mortalities for RIR, BY, and DW chicks were 25.1%, 8.3%, and 22.7%, respectively, and the corresponding carrier-states in the spleens were 17.9%, 0.6%, and 15.8%. Survival and carrier-state heritabilities were estimated using an animal threshold model. Survival heritability was 0.197, 0.091, and 0.167 in RIR, BY, and DW populations, respectively, and the heritabilities of carrier state for DW and RIR were 0.32 and 0.16, respectively. This is the first time that the heritability of the SP carrier state has been evaluated in chickens. Our study provides experimental evidence that chickens with various genetic background exhibited significantly different SP-resistant activities and heritabilities. These results may be useful for selecting lines with better disease resistance.
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/21/18 03:49 PM

Naturally Occurring Frame-Shift Mutations in the tvb Receptor Gene Are Responsible for Decreased Susceptibility of Chicken to Infection with Avian Leukosis Virus Subgroups B, D, and E.



The group of highly related avian leucosis viruses (ALVs) in chickens thought to have evolved from a common retroviral ancestor into six subgroups, A to E and J. These ALV subgroups use diverse cellular proteins encoded by four genetic loci in chickens as receptors to gain entry into host cells. Host exposed to ALVs might be under selective pressure to develop resistance to ALVs infection. Indeed, the resistant alleles have previously been identified in all four receptor loci in chicken. The tvb gene encodes a receptor, which determines the susceptibility of host cells to the subgroups B, D, and E ALV. We herein describe the identification of two novel alleles of tvb receptor gene, which possess independent insertions each within the exon 4. The insertions resulted in frame-shift mutations reveal a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the production of truncated Tvb protein. As a result, we observed that the frame-shift mutations in the tvb gene significantly lower the binding affinity of the truncated Tvb receptors for the ALV-B, ALV-D and ALV-E envelope glycoproteins, and significantly reduce susceptibility to infection by ALV-B, ALV-D and ALV-E in vitro and in vivo Taken together, these findings are suggestive for frame-shift mutation can be a molecular mechanism of reduction of susceptibility to ALV and enhance our understanding of virus-host coevolution.IMPORTANCE Avian leukosis virus (ALV) once caused devastated economic loss to the U.S. poultry industry prior the current eradication schemes in place, and continues causing severe calamity to the poultry industry in China and Southeast Asia, where deployment of a complete eradication scheme remains a challenge. The tvb gene encodes the cellular receptor necessary for the subgroup B, D, and E ALV infection. Two tvb allelic variants resulted from frame-shift mutations have been identified in this study, which have been elucidated with significantly reduced functionality in mediating the subgroups B, D, and E ALV infection. Unlike the control of herpesvirus-induced diseases by vaccination, the control of avian leukosis in chickens has been totally relying on virus eradication measures and host genetic resistance. This finding enriches the allelic pool of tvb gene, and expands the potentiality for genetic improvement of ALV resistance in varied chicken populations by selection.


Acquisition of resistance to avian leukosis virus subgroup B through mutations on tvb cysteine-rich domains in DF-1 chicken fibroblasts.



Avian leukosis virus (ALV) is a retrovirus that causes tumors in avian species, and its vertical and horizontal transmission in poultry flocks results in enormous economic losses. Despite the discovery of specific host receptors, there have been few reports on the modulation of viral susceptibility via genetic modification. We therefore engineered acquired resistance to ALV subgroup B using CRISPR/Cas9-mediated genome editing technology in DF-1 chicken fibroblasts. Using this method, we efficiently modified the tumor virus locus B (tvb) gene, encoding the TVB receptor, which is essential for ALV subgroup B entry into host cells. By expanding individual DF-1 clones, we established that artificially generated premature stop codons in the cysteine-rich domain (CRD) of TVB receptor confer resistance to ALV subgroup B. Furthermore, we found that a cysteine residue (C80) of CRD2 plays a crucial role in ALV subgroup B entry. These results suggest that CRISPR/Cas9-mediated genome editing can be used to efficiently modify avian cells and establish novel chicken cell lines with resistance to viral infection.
Posted by: Wieslaw

Re: Avian leucosis, Marek's & other diseases - 01/23/18 02:54 PM

One more article on avian flu

Posted by: Redcap

Re: Avian leucosis, Marek's & other diseases - 02/20/18 11:40 AM