D9195.PDF

Rev. sci. tech. Off. int. Epiz., 1 9 9 8 , 1 7 (1), 249-255
Genetic resistance to avian viruses
N. Bumstead
Institute for Animal Health, Agricultural and Food Research Council, Compton Laboratory Compton
Nr Newbury, Berkshire RG16 ONN, United Kingdom
Summary
V i r a l i n f e c t i o n s of poultry c a n b e c a t a s t r o p h i c in t e r m s of both w e l f a r e a n d
e c o n o m i c s , and a l t h o u g h v a c c i n e s h a v e b e e n v e r y s u c c e s s f u l in c o m b a t i n g t h e s e
d i s e a s e s , n e w f o r m s of v i r u s e s h a v e e v o l v e d w h i c h p r e s e n t i n c r e a s i n g difficulties
for v a c c i n e control. D i f f e r e n c e s in g e n e t i c susceptibility are k n o w n t o exist for
m a n y of t h e m a j o r viral p a t h o g e n s of poultry. C o n s e q u e n t l y , a n i n c r e a s e in t h e
level of g e n e t i c r e s i s t a n c e p r o v i d e s a possible m e a n s of e n h a n c i n g p r o t e c t i o n of
f l o c k s . This is p a r t i c u l a r l y f e a s i b l e w h e r e specific r e s i s t a n c e g e n e s h a v e b e e n
identified, a s in t h e c a s e of avian leukosis a n d M a r e k ' s d i s e a s e , a n d t h e
d e v e l o p m e n t of g e n e t i c m a p s of t h e c h i c k e n has o f f e r e d n e w possibilities for t h e
identification of f u r t h e r r e s i s t a n c e g e n e s . It h a s also b e c o m e c l e a r t h a t t h e r e a r e
g e n e t i c d i f f e r e n c e s in t h e r e s p o n s e t o live a t t e n u a t e d v a c c i n e v i r u s e s , a n d n e w
possibilities exist t o m a n i p u l a t e t h e g e n e t i c s o f host f l o c k s so t h a t t h e e f f e c t of
v a c c i n a t i o n c a n be o p t i m i s e d .
Keywords
A v i a n leukosis - Disease resistance - Fowl - Genetics - M a r e k ' s disease - Susceptibility
-Viruses.
Introduction
The scale of modern poultry husbandry has generated a
situation in which flocks suffer from a limited number of
pathogens, but the effects of these in any particular flock can
be catastrophic. This is particularly the case for viral
infections: for example, infections with Marek's disease in
unvaccinated flocks can kill 4 0 % or more of the flock. Other
viral infections, such as infectious bursal disease (Gumboro
disease) and avian infectious bronchitis virus, can cause
infections of comparable severity, while avian retroviruses
cause more insidious disease. Vaccines generated by
attenuating these viruses have been very successful in
controlling these diseases. However, losses still occur, and
there is evidence for the emergence, if not the evolution, of
increasingly pathogenic variants of several of the viruses,
which are able to overcome previously successful vaccines (4,
48). While improved vaccines have been produced, there are
limits to the extent to which attenuation can be reduced
before the vaccine itself becomes harmful, and other means of
controlling infection - or enhancing the effect of vaccines can only be helpful.
provided two of the earliest examples of such resistance in
animals. In the case of these two viruses, selection for
resistance has contributed to control measures, and although
the mechanism of this resistance is still not understood, the
association of resistance to Marek's disease with the major
histocompatibility complex (MHC) still provides the strongest
example of an association between the MHC and disease.
Nevertheless, in most cases the genes responsible for genetic
resistance are unknown. In principle, the selection of birds
with higher levels of resistance by assessment of the response
to infection through progeny testing is possible, but in reality
this is impracticable. Any widespread application of selection
for genetic resistance will be dependent on the identification
of either the genes responsible, or at least of closely linked
genetic markers. The recent development of genetic maps of
the chicken genome ( 1 0 , 13, 3 3 ) , and
the associated
technologies for identifying and isolating genes b y positional
cloning, provide a new means of identifying resistance genes.
The current state of the genomic map can be viewed at the
Roslin Institute W e b site (http://ri.bbsrc.uk). Several research
groups are now applying these technologies to identify disease
resistance genes. Similar techniques are being used in other
species, particularly in mice, to identify resistance genes
Differences have been noted in the susceptibility of chickens
which may be equally important in chickens ( 5 , 19, 4 3 ) .
to many of the principal viral pathogens of poultry, and
Chickens are particularly suitable for genetic mapping of these
resistance to Marek's disease virus and avian leukosis virus
disease resistance genes, due to the potential which exists in
250
Rev. sci. tech. Off. int. Epiz., 17(1]
the poultry industry to investigate large groups of defined
progeny in relatively homogeneous environments. In
addition, chicken diseases and the pathogens which cause
them have been studied in depth.
Besides the existence of genetic differences in innate
susceptibility to disease, differences have also been noted in
the response of chickens to vaccines. Selection of chickens
which respond particularly well (or particularly uniformly) to
vaccination offers another route to greater disease protection.
This article will summarise the current state of knowledge of
resistance genes in poultry and the possibilities which exist for
further identifying resistance genes.
Resistance to Marek's disease
Differences in genetic resistance to Marek's disease were first
established by the early work of Cole (16). Cole subsequently
showed strong responses to selection after only two
generations, which suggested a simple genetic control ( 1 6 ) .
Hanson first reported an association between disease
resistance and the chicken MHC ( 2 8 ) , and this was rapidly
confirmed by Longenecker et al. (34) and Briles et al. (7). This
association
remains
the
clearest
example
relating
polymorphism in the MHC complex to differences in disease
susceptibility, although similar associations have since been
found in mammals.
Although the MHC region has now been clearly shown to
contain many genes likely to affect the immunological
response to disease, the majority of these are so closely linked
as to be inherited as a single unit (a haplotype), and hence
effectively as a single gene. In the past, MHC haplotypes in
chickens were identified using specific antisera to agglutinate
red blood cells, an extremely cheap and efficient identification
procedure ( 4 4 ) . However, Pink et al. showed that these
antibodies principally identify the B-G complex of cell surface
glycoproteins linked to the MHC, rather than the MHC itself
(38). Briles et al. were able to show that resistance was
associated with the classical MHC rather than the B-G region
(8), but the lack of identified recombinants within the MHC
itself has prevented further genetic dissection of the region to
identify the specific resistance gene within the MHC complex.
Extensive sequence data obtained from the MHC region have
identified chicken homologues of the principal mammalian
MHC genes and have opened up extensive possibilities for
new methods of MHC typing, using either restriction
fragment polymorphisms or polymerase chain reaction
(PCR)-based assays ( 2 6 , 2 7 ) .
in the degree of susceptibility to Marek's disease.
Immunological comparisons between these lines have
identified differences but have not suggested a convincing
explanation for the variation in resistance ( 3 9 ) . However,
cross-immunisations of lymphocytes between the lines have
identified three lymphocyte surface antigens (Bu-1, Thy-1 and
Ly-4) which all demonstrate a degree of association with
resistance (22, 2 4 ) . Only the gene coding for Bu-1 has been
isolated to date (45). This gene, now designated CHB6, is a
highly glycosylated membrane protein expressed on chicken
B lymphocytes through most of their development. The gene
is polymorphic between lines 6 and 7 and shows a
significant association with resistance in crosses between these
lines, although it accounts for only a small proportion of the
difference in resistance between the lines ( 4 5 ) . To date, no
mammalian homologue of the gene has been identified, and
the mechanism of resistance remains unknown.
1
A quantitative PCR assay has recently been developed which
allows the replication of Marek's disease virus in infected
tissues to be assessed throughout infection (12). Comparisons
of viral replication in inbred line N (a line homozygous for a
resistant MHC haplotype), line 6 and line 7 show very
different patterns through the course of infection
(N. Bumstead, unpublished results) (Fig.l).
l
X
2
2
Fig. 1
Numbers of Marek's disease genomes per cell for resistant and
susceptible inbred lines of chickens
The susceptible line 7 birds show much higher levels of viral
load from the very early stages of infection, a condition which
persists until eventual death from tumour development. In
contrast, the resistant lines show much lower levels of viral
replication, which in the case of line 6 peak fall below
detectable levels. Birds of line N have low viral levels
throughout, but these levels persist at a stage when virus is no
longer detectable in line 6 birds. In F 2 crosses between lines
6 and 7 , birds with higher viral levels early in infection were
more likely to develop tumours subsequently. Thus it seems
probable that a significant element of the genetic resistance,
whether MHC-associated or non-MHC-associated, is due to
control of viral replication in the early stages of infection. This
2
l
1
Although the MHC haplotypes make a substantial
contribution to resistance to Marek's disease, other genes also
contribute to resistance, and these have been extensively
investigated in comparisons between inbred lines 6 and 7 .
These lines share a common MHC haplotype but differ greatly
2
1
2
Rev. sci. tech. Off. int. Epiz., 17 (1 )
resembles the genetic resistance seen for cytomegalovirus in
mice, which is also reflected in differences in viral replication,
and for which there is also both MHC- and non-MHCassociated resistance ( 2 5 ) . In mice, a strong resistance gene,
Cmvl, has been mapped to the natural killer (NK) region of
chromosome 6 ( 2 1 , 4 3 ) . Precisely which gene within this
region is responsible for resistance has not yet been identified;
however, it is known to affect NK cell activity ( 4 2 ) . The
responsible gene most probably corresponds to one of the
receptors present in this region which both enhance and
control NK activity ( 3 2 , 4 9 ) .
Attempts are now underway to map the non-MHC-associated
Marek's disease-resistance genes in chickens, and preliminary
results have identified a number of candidate resistance genes
(H.
Cheng, personal communication; N. Bumstead,
unpublished results).
Resistance to avian leukosis
virus
The
best understood example of genes influencing
susceptibility to viral infection in chickens are the genes which
code for the receptors for avian leukosis viruses (ALV). ALVs
can be divided into subgroups on the basis of viral envelope
properties ( 2 9 , 4 6 , 4 7 ) . The A and B subgroups (15) occur as
common pathogenic viruses in the field and are a cause of
reduced growth rate or egg production (23). Susceptibility to
infection for A and B subgroups is inherited in each case as a
single dominant gene, which represents the cellular receptor
for that subgroup of virus ( 3 5 , 4 1 ) . Selection for resistant
genotypes by inoculation of the chorioallantoic membrane of
eggs with a Rous sarcoma virus pseudotype (a laboratory
strain of related virus adapted to have the characteristic
envelope protein of the A or B subgroups of ALV) generates
transformed pocks on the membrane of susceptible embryos.
Although potentially capable of discriminating resistant and
susceptible embryos, this process is laborious, can be prone to
error and involves substantial progeny testing. Improved
methods for identifying resistant birds have been developed,
culminating in the recent identification and cloning of the
receptor for the A subgroup virus (50). The receptor has now
been shown to be related to the low density lipoprotein
receptor ( 3 ) . Identification of the receptor opens up the
possibility of accurate identification of genotypes by DNA
screening, though selection has been largely superseded by
eradication of the virus from breeding flocks by virological
testing. The extent to which ALV infects flocks derived from
the breeding flocks is unknown, and there is some concern
that since parental flocks no longer secrete maternal antibody
and are not subject to selection for resistance, these flocks may
be inadequately protected.
Exogenous retroviral infections have also given rise to
endogenous retroviral genomes embedded in chicken
chromosomes and inherited as chicken genes, which in some
251
cases express viral proteins or, rarely, infectious virus
(reviewed by Crittenden [18]). Endogenous viral genomes
which express the viral coat protein can block exogenous
infection by viruses of the same subgroup, and thus provide a
form of resistance ( 6 ) .
A new, recently identified form of ALV has a novel envelope
protein and is now widespread in commercial flocks ( 3 6 ) .
This apparently new virus subgroup appears to be a
recombinant between the exogenous virus and
an
endogenous viral genome ( 2 ) . No chickens resistant to
infection by this new virus have been identified to date.
Resistance to infectious bursal
disease (Gumboro disease)
Infectious bursal disease (Gumboro disease) virus (IBDV) is a
birnavirus, with a simple bi-segmented double-stranded RNA
genome. The virus shows extreme specificity for maturing B
lymphocytes and causes a cytolytic infection of these cells,
particularly in the bursa of Fabricius in three-to five-week-old
birds. Although IBDV infection can cause mortality, greater
losses occur through the damage caused by infection to the
immune system, which allows subsequent infection by other
pathogens and reduces the effectiveness of vaccination.
Comparisons between inbred lines of chickens show large
differences in susceptibility of different genotypes to the
disease (Fig. 2 ) . Some lines show little or no mortality and
limited damage to bursal lymphocytes, while the BrL (Brown
Leghorn) line in particular showed high levels of mortality
and extreme destruction of the bursa, even in surviving birds
(11). In crosses between resistant and susceptible lines,
resistance was inherited as a dominant trait. Inheritance of
resistance in these crosses, the extreme tissue specificity of the
virus, the simplicity of the viral genome and the very rapid
and short-lived nature of the infection all suggest that
resistance might be due to a very small number of genes.
However, the genes responsible are unknown at present.
Fig. 2
Mortality of inbred lines of chickens following infection with
infectious bursal disease (Gumboro disease) virus
252
Resistance to avian infectious
bronchitis
Avian infectious bronchitis virus (IBV) is a cause of acute
respiratory disease in chickens. Infection with IBV causes
damage to the trachea; secondary bacterial infection of the
damaged tissue can then cause asphyxiation and death.
Comparison of inbred lines showed large differences in
susceptibility to the trait (Fig. 3 ) . The differences between the
inbred lines were inherited in crosses between resistant and
susceptible lines and were similar whether virus alone, or a
combination of viruses and pathogenic bacteria, was
inoculated (9). There were only small differences in resistance
when bacteria were inoculated alone, which did not correlate
with resistance to IBV, so that the differences seen with viral
infection are likely to reflect differences in the damage caused
by IBV itself. Comparison of the replication of IBV in the
visceral tissues of resistant and susceptible birds showed little
variation between the host genotypes ( 1 7 ) , which suggests
that resistance affects the extent of the disease at the primary
site of the infection in the trachea. In mice, resistance to the
equivalent murine coronaviruses has been ascribed to cellular
receptors ( 1 4 ) , but these have not yet been identified in
chickens.
Rev. sci. tech. Off. int. Epiz., 17 (1|
Fadly and Bacon and Bumstead et al. have shown similar
differences in response to vaccines for infectious bursal
disease, which may also be due to the interaction of vaccine
and the MHC (11,
20).
At present there is no clear indication of whether these
differences in response are due to differences in MHC
presentation by either the class I or class II molecules, but this
is
an
exciting possibility. The importance
of antigen
presentation and the peptide-binding specificity of the MHC
has been demonstrated in mammals ( 4 0 ) and is likely to be
similar in chickens ( 3 0 , 3 7 ) . Indeed, since the chicken MHC
appears to be simpler and reduced relative to mammalian
MHCs, these differences may be correspondingly greater (31).
The possibility exists of improving the level and consistency of
response to vaccination by selection of the host MHC, and the
importance of these genetic differences can only increase with
the advent of simplified molecular vaccines.
Conclusion
Current knowledge of genetic resistance to viral diseases in
birds is at an early but exciting stage. There is sufficient
information to suggest that large differences in susceptibility
exist for many, if not all, of the major diseases of poultry, but
in most cases little is known of the genes that are responsible
for these differences in resistance. However, recent advances
in molecular biology have transformed the possibilities for
identifying these genes. To an even greater extent, the
development
of genomic mapping
should
enable the
identification of many of these genes, either directly in
chickens or by identifying chicken homologues of genes
mapped in other species. Once resistance genes have been
identified, selection for those genes in poultry flocks should
be possible. Identification of function of the genes may also
suggest other methods of pharmacological or immunological
control.
Fig. 3
Mortality in inbred lines of chickens following infection with avian
infectious bronchitis virus
There is already very extensive understanding of avian viral
pathogens, and if this knowledge can be allied to detailed
understanding of the mechanisms of host resistance to
Genetic differences in response
to vaccines
In addition to the genetic differences in resistance described
above, there is also evidence that chickens vary in response to
the attenuated viruses currently used as vaccines. Bacon and
Witter have shown MHC-related differences in the protection
of birds vaccinated with different Marek's disease vaccine
strains (1). Different MHC haplotypes responded best to
vaccination with each of the three different categories of
vaccine strain (attenuated pathogenic virus, naturally
occurring non-pathogenic virus or herpesvirus of turkeys).
disease, poultry should provide an ideal environment in
which to study the interaction and evolution of viruses and
their hosts. This is particularly the case for the MHC, which
plays a strong role both in innate resistance and response to
vaccines in chickens. The recent advances in understanding
the function of MHC molecules and the organisation of the
chicken MHC suggest that the identification and utilisation of
the molecular mechanisms underlying these associations
should soon be possible.
253
Rev. sci. tech. Off. int. Epiz., 17(1)
Résistance génétique aux virus aviaires
N. Bumstead
Résumé
Les i n f e c t i o n s v i r a l e s a v i a i r e s p e u v e n t e n t r a î n e r
des
conséquences
c a t a s t r o p h i q u e s sur le plan é c o n o m i q u e c o m m e sur celui du b i e n - ê t r e a n i m a l e t
m ê m e si d e s v a c c i n s se s o n t a v é r é s t r è s e f f i c a c e s d a n s la lutte c o n t r e c e s
m a l a d i e s , de n o u v e l l e s f o r m e s de virus s o n t a p p a r u e s qui r e n d e n t c e t y p e de
p r o p h y l a x i e de plus e n plus difficile. On sait qu'il existe d e s d i f f é r e n c e s de
sensibilité g é n é t i q u e à n o m b r e d ' a g e n t s p a t h o g è n e s p a r m i les plus i m p o r t a n t s
pour les volailles. Le r e n f o r c e m e n t de la r é s i s t a n c e g é n é t i q u e c o n s t i t u e d o n c un
m o y e n potentiel d ' a m é l i o r e r la p r o t e c t i o n d e s é l e v a g e s . Ceci est n o t a m m e n t
possible lorsque d e s g è n e s de r é s i s t a n c e s p é c i f i q u e ont é t é identifiés, c o m m e
c ' e s t le c a s pour la l e u c o s e aviaire et pour la m a l a d i e de M a r e k , e t l ' é t a b l i s s e m e n t
d e c a r t e s g é n é t i q u e s pour les volailles d e v r a i t p e r m e t t r e d'identifier d ' a u t r e s
g è n e s de r é s i s t a n c e . Il est, par ailleurs, é v i d e n t qu'il existe d e s d i f f é r e n c e s
g é n é t i q u e s pour ce qui e s t d e la r é p o n s e a u x v a c c i n s à virus v i v a n t s a t t é n u é s , e t
les n o u v e l l e s possibilités de m a n i p u l a t i o n g é n é t i q u e p o u r r a i e n t p e r m e t t r e
d'optimiser les effets de la v a c c i n a t i o n c h e z les volailles.
Mots-clés
Génétique - Leucose aviaire - M a l a d i e de M a r e k - Résistance aux maladies - Sensibilité
-Virus-Volailles.
Resistencia genética a los virus aviares
N. Bumstead
Resumen
Las i n f e c c i o n e s v í r i c a s d e las a v e s d e c o r r a l p u e d e n r e s u l t a r c a t a s t r ó f i c a s , t a n t o
e n t é r m i n o s e c o n ó m i c o s c o m o de b i e n e s t a r a n i m a l . A u n q u e el uso de v a c u n a s se
ha r e v e l a d o m u y e f i c a z p a r a c o m b a t i r e s e tipo de e n f e r m e d a d e s , e n los últimos
t i e m p o s h a n h e c h o a p a r i c i ó n n u e v o s tipos de virus cuyo control por v a c u n a c i ó n
p l a n t e a c r e c i e n t e s d i f i c u l t a d e s . S e s a b e q u e , p a r a m u c h o s de los p r i n c i p a l e s
p a t ó g e n o s víricos q u e a f e c t a n a las a v e s d e c o r r a l , e x i s t e n d i f e r e n c i a s d e
s u s c e p t i b i l i d a d de o r i g e n g e n é t i c o . En este s e n t i d o , un posible m é t o d o p a r a
p r o t e g e r c o n m á s e f i c a c i a a las b a n d a d a s c o n s i s t e en a c r e c e n t a r el nivel de
r e s i s t e n c i a g e n é t i c a . Ello resulta e s p e c i a l m e n t e f a c t i b l e c u a n d o se h a n
i d e n t i f i c a d o p r e v i a m e n t e g e n e s q u e c o n f i e r e n r e s i s t e n c i a , c o m o o c u r r e c o n la
l e u c o s i s aviar o la e n f e r m e d a d d e M a r e k . Por otro l a d o , la e l a b o r a c i ó n d e m a p a s
g e n é t i c o s de los pollos ha a b i e r t o las p u e r t a s a la i d e n t i f i c a c i ó n de otros g e n e s de
r e s i s t e n c i a . S e ha o b s e r v a d o a s i m i s m o q u e e x i s t e n d i f e r e n c i a s g e n é t i c a s e n la
r e s p u e s t a de los a n i m a l e s a las v a c u n a s c o n virus vivos a t e n u a d o s , h e c h o q u e
s u g i e r e n u e v a s posibilidades p a r a m a n i p u l a r la d o t a c i ó n g e n é t i c a d e las
b a n d a d a s h u é s p e d e s y optimizar así los e f e c t o s d e la v a c u n a c i ó n .
Palabras clave
Aves de corral - Enfermedad de M a r e k - Genética - Leucosis aviar - Resistencia a la
e n f e r m e d a d - S u s c e p t i b i l i d a d - Virus.
254
Rev. sci. tech. Off. int. Epiz., 17 (1)
References
1. Bacon L.D. & Witter R.L. (1994). - B haplotype influence on
the relative efficacy of Marek's disease vaccines in commercial
chickens. Poult. Sci., 73 (4), 481-487.
2. Bai J . , Payne L.N. & Skinner M.A. (1995). - HPRS-103
(exogenous avian leukosis virus, subgroup J ) has an env gene
related to those of endogenous elements EAV-0 and E51 and
an E element found previously only in sarcoma viruses.
J. Virol, 69 (2); 779-784.
3. Bates P., Young A.T. & Varmus H.E. (1993). - A receptor for
subgroup A Rous sarcoma vims is related to the low density
lipoprotein receptor. Cell, 74 (6), 1043-1051.
4. Baxendale W. (1996). - Current methods of delivery of
poultry vaccines. In Poultry immunology (T.F. Davison,
T.R. Morris & L.N. Payne, eds). Carfax Publishing Company,
Abingdon, United Kingdom, 375-387.
5. Bernasconi D., Schultz U. & Staehli P. (1995). - The
interferon-induced Mx protein of chickens lacks antiviral
activity. J. Interferon Cytokine Res., 15, 47-53.
6. Best S., Le Tissier P., Towers G. & Stoye J.P. (1996). Positional cloning of the mouse retrovirus restriction gene
Fvl. Nature, 382 (6594), 826-829.
16. Cole R.K. (1968). - Studies on genetic resistance to Marek's
disease. Avian Dis., 12, 9-28.
17. Cook J.K.A., Huggins M.B. & Burnstead N. (1990). Investigations into the resistance of chicken lines to infection
with infectious bronchitis virus. In Coronaviruses and their
diseases (D. Cavanagh & T.D.K. Brown, eds). Plenum Press,
New York, 491-496.
18. Crittenden L.B. (1991). - Retroviral elements in the genome
of the chicken: implications fo poultry genetics and breeding.
Crit. Rev. Poult. Biol, 3, 73-109.
19. Delano M.L. & Brownstein D.G. (1995). - Innate resistance
to lethal mousepox is genetically linked to the NK gene
complex on chromosme 6 and correlates with early restriction
of virus replication by cells with an NK phenotype. J. Virol,
69 (9), 5875-5877.
20. Fadly A.M. & Bacon L.D. (1992). - Response of B congenic
chickens to infection with infectious bursal disease vims.
Avian Dis., 36 (4), 871-880.
7. Briles W.E.', Stone H.A. & Cole R.K. (1977). - Marek's
disease: effects of B histocompatibility alloalleles in resistant
and susceptible chicken lines. Science, 195, 193-195.
21. Forbes C.A., Brown M.G., Cho R., Shellam G.R., Yokoyama
W.M. & Scalzo A.A. (1997). - The Cmvl host resistance locus
is closely linked to the Ly49 multigene family within the
natural killer cell gene complex on mouse chromosome 6.
Genomics, 4 1 , 406-413.
8. Briles W.E., Briles R.W., Tafts R E . & Stone H.A. (1983). Resistance to a malignant lymphoma in chickens is mapped
to a subregion of the major histocompatibility (B) complex.
Science, 219, 977-979.
22. Fredericksen T.L., Longenecker B.M., Pazderka F.,
Gilmour D.G. & Ruth R.F. (1977). - A T-cell antigen system
of chickens: Ly-4 and Marek's disease. Immunogenetics, 5,
535-552.
9. Bumstead N., Huggins M.B. & Cook J.K.A. (1989). - Genetic
differences in susceptibility to a mixture of avian infectious
bronchitis vims and Escherichia coli. Br. Poult. Sci, 30, 39-48.
10. Bumstead N. & Palyga J. (1992). - A preliminary linkage map
of the chicken genome. Genomics, 13, 690-697.
11. Bumstead N., Reece R.L. & . Cook J.K.A. (1993). - Genetic
differences in susceptibility of chicken lines to infectious
bursal disease vims. Poult. Sci., 72, 189-193.
12. Bumstead N., Sillibourne J . , Rennie M., Ross N. &
Davison T.F. (1997). - Quantification of Marek's disease vims
in chicken lymphocytes using the polymerase chain reaction
with fluorescence detection, J. virol Meth., 65, 75-81.
13'. Burt D., Bumstead N., Bitgood J.J., Ponce de León FA. &
Crittenden L.B. (1995). - Chicken genome mapping: a new
era in avian molecular genetics. Trends Genet., 11, 190-194.
14. Buschman E. & Skamene E. (1995). - Genetic resistance to
coronavirus infection: a review. Adv. expl med. Biol, 380,
1-11.
15. Calnek B.W. (1968). - Lymphoid leukosis virus: a survey of
commercial breeding flocks for genetic resistance and
incidence of embryo infection. Avian Dis., 12, 104-111.
23. Gavora J.S., Spencer J.L., Gowe R.S. & Harris D.L. (1980). Lymphoid leukosis virus infection: effects on production and
mortality and consequences in selection for high egg
production. Poult. Sci, 59, 2165-2178.
24. Gilmour D.G., Brand A , Donnelly N. & Stone H.A. (1976). Bu-1 and Thy-1. Two loci determining surface antigens of B or
T lymphocytes in the chicken. Immunogenetics, 3, 549-563.
25. Grundy J.E., Mackenzie J.S. & Stanley N.F. (1981). Influence of H-2 and non H-2 genes on resistance to murine
cytomegalovirus infection. In/ect. Immun., 32, 277-286.
26. Guillemot F., Billault A., Pourquié O., Béhar G.,
Chaussé A.M., Zoorob R., Kreibich G. & Auffray C. (1988). A molecular map of the chicken major histocompatibility
complex: the class II (3 genes are closely linked to the class I
genes and to the nucleolar oganiser. EMBO J., 7, 2775-2785.
27. Guillemot F., Billault A., Pourquié O., Béhar G.,
Chaussé A.M., Zoorob R., Kreibich G. & Auffray C. (1989). Physical linkage of a guanine
nucleotide-binding
protein-related gene to the chicken major histocompatibility
complex. Proc. natl Acad. Sci. USA, 86, 4594-4598.
Rev. sci. tech. Off. int. Epiz., 17 (1)
28. Hanson M.P., Van Zandy J.N. & Law G.R.J. (1967). Differences in susceptibility to Marek's disease in chickens
carrying two different B locus blood alleles. Poult. Sci., 4 6 ,
1268.
29. Hunter E. (1997). - Viral entry and receptors, In Retroviruses
(J.M. Coffin, S.H. Hughes & H.E. Varmus, eds). Cold Spring
Harbor Laboratory Press, New York, 71-119.
30. Kaufman J . , Andersen R., Avila D., Engberg J . , Lambris J . ,
Salomomsen J., Welinder K. & Skjodt K. (1992). - Different
features of the MHC class I heterodimer have evolved at
different rates: chicken B-F and B2-microglobulin sequences
reveal invariant surface residues. J. Immunol, 148,
1532-1546.
31. Kaufman J . , Volk H. & Wallny H.-J. (1995). - A 'minimal
essential Mhc' and an 'unrecognized Mhc': two extremes in
selection for polymorphism. Immunol Rev., 143, 63-68.
32. Lanier L.L. & Phillips J.H. (1996). - Inhibitory MHC class 1
receptors on NK cells and T cells. Immunol Today, 17 (2),
86-91.
255
40. Rammenssee H.G., Falk K. & Rotzschke O. (1993). - MHC
molecules as peptide receptors. Curr. Opin. Immunol, 5 (1),
35-44.
41. Rubin H. (1965). - Genetic control of cellular susceptibility
to pseudotypes of Rous sarcoma virus. Virology, 2 6 , 270-276.
42. Scalzo A.A., Fitzgerald N.A., Wallace C.R., Gibbons A.E.,
Cheng Smart Y., Burton R.C. & Shellam G.R. (1992). - The
effect of the Cmv-1 resistance gene, which is linked to the
natural killer cell gene complex, is mediated by natural killer
cells. J. Immunol, 149 (2), 581-589.
43. Scalzo A.A., Lyons P.A., Fitzgerald N.A., Forbes C.A.,
Yokoyama W.M. & Shellam G.R. (1995). - Genetic mapping
of Cmvl in the region of mouse chromosome 6 encoding the
NK gene complex-associated loci Ly49 and musNKR-Pl.
Genomics, 27, 435-441.
44. Schierman L.W. & Nordskog A.W. (1961). - Relationship of
blood type to histocompatibility in chickens. Science, 134,
1008-1009.
33. Levin L, Santangelo L., Cheng H., Crittenden L.B. &
Dodgson J.B. (1994). - An autosomal linkage map of the
chicken. J. Hered., 8 5 , 79-85.
45. Tregaskes C.A., Bumstead N., Davison T.F. & Young J.R.
(1996). - Chicken B-cell marker chB6 (Bu-1) is a highly
glycosylated protein of unique structure. Immunogenetics, 44,
212-217.
34. Longenecker B., Pazderka F., Gavora J.S., Spencer J.L. &
Ruth R.F. (1976). - Lymphoma associated induced by herpes
virus: resistance associated with a major histocompatibility
complex gene, Immunogenetics, 3, 401-407.
46. Vogt P.K. & Ishizaki R. (1965). - Reciprocal patterns of
genetic resistance to avian tumour viruses in two lines of
chickens. Virology, 26, 664-672.
35. Payne L.N. & Biggs P.M. (1966). - Genetic basis of cellular
susceptibility to the Schmidt-Ruppin and Harris strains of
Rous sarcoma virus. Virology, 29, 190-198.
47. Vogt P.K. & Ishizaki R. (1966). - Patterns of viral interference
in the avian leukosis and sarcoma complex. Virology, 30,
368-374.
36. Payne L.N., Brown S.R., Bumstead N., Howes K., Frazier J.A.
& Thouless M.E. (1991). - A novel subgroup of exogenous
avian leukosis virus in chickens. J. gen. Virol, 72, 801-807.
48. Witter R.L. (1997). - Increased virulence of Marek's disease
virus field isolates. Avian Dis., 41 (1), 149-163.
37. Pharr G.T., Hunt H.D., Bacon L.D. & Dodgson J.B. (1993). Identification of class II major histocompatibility complex
polymorphisms predicted to be important in peptide antigen
presentation. Poult. Sci., 72 (7), 1312-1317.
38. Pink J.R.L., Droege W., Hala K., Miggiano V.C. & Ziegler A.
(1977). - A three-locus model for the chicken major
histocompatibility complex. Immunogenetics, 5, 203-210.
39. Powell P.C., Hartley K.J., Mustill B. & Rennie M. (1983). Studies on the role of macrophages in Marek's disease of the
chicken, j . Reticuloendothel. Soc, 34 (4), 289-297.
49. Yabe T., McSherry C , Bach F.H., Fisch P., Scali R.P., Sondel
P.M. & Houchins J.P. (1993). - A multigene family on human
chromosome 12 encodes natural killer-cell lectins.
Immunogenetics, 37, 455-460.
50. Young A.T., Bates P. & Varmus H.E. (1993). - Isolation of a
gene that confers susceptibility to infection by subgroup A
avian leukosis and sarcoma viruses. J . Virol, 67 (4),
1811-1816.