Avian leukosis/ sarcoma virus infections - status and socio-economic impact revisited

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1 Indian J. Poult. Sci. (2007) 42(3): ; Review Article Avian leukosis/ sarcoma virus infections - status and socio-economic impact revisited ALKA TOMAR* AND V.K. SAXENA Tumor Immunology Laboratory / Virus Laboratory, Indian Veterinary Research Institute, Izatnagar (U.P.) Received : November 13, 2007 Accepted : December 12, 2007 ABSTRACT Avian leukosis/sarcoma viruses (AL/SV) infect large segments of modern poultry industry, hence are also present in commercial chickens and eggs that widely expose humans on a consistent basis. Horizontal/contact transmission pattern maintains a rate of vertical/congenital transmission of exogenous (infectious) virus from one generation to next, giving rise to avian leukosis virus (ALV) or group specific antigen (gsag) shedding chickens (shedders); thus, a permanent source of infection at the farm. Genetically transmitted endogenous (majorly non-infectious sequences) virus may or may not be expressed; and believed to be not shed or shed at low levels. Final outcome of AL/SV infections depends on interaction of exogenous viruses with that of endogenous viruses or their sequences in a chicken host. AL/SV infections include a variety of transmissible benign and malignant neoplastic conditions, nonneoplastic conditions, and subclinical infections. Avian leukosis, a list C disease, is the most common disease seen in field flocks; recently though, myeloid leukosis has become more prevalent. Economic losses due to ALV tumor mortality and reduced productivity due to subclinical infections are estimated to be millions of US dollars each year. Shedder hens are characteristically lower, than gsag non-shedding hens, in fitness traits, reproductive traits and performance traits. Diagnostic procedures consist of both direct and indirect biological, molecular and serological assays. Direct assay of viral major gsag or p27 by an enzyme linked immunosorbent assay (ELISA) is the most common biological assay to determine presence of AL/SV, but p27 is shared by both exogenous and endogenous viruses, hence can not be used to differentiate between the two groups of viruses. Additionally, most of the biological assays are cumbersome and time- consuming; and even the most sensitive biological assay may not identify all the infected dams. Molecular assays are costly and unsuitable for field conditions; and serological assays only help identification of viral envelope subgroups. Therefore, an urgent need is felt for development of an alternate antigen for convenient, precise and early diagnosis of AL/SV infections in poultry flocks with objective to reduce incidence of ALV infection in general. Current programs for control and eradication of AL/SV infections in chicken breeder flocks are based on selective breeding and elimination of dams that test positive for the virus, breaking vertical transmission of the virus from dam to progeny and early detection and removal of virus shedding birds to reduce spread of congenital and contact infections in other birds. Recent reports of public health significance of AL/SV infections with regard to consumption of chicken origin products, contamination of chicken origin live virus vaccines of humans and animals and emergence of new viruses from "parent" AL/SV have been alarming and need immediate attention. Key words : Avian leukosis/ sarcoma virus, exogenous virus, endogenous virus, group specific antigen, enzyme linked immunosorbent assay Avian leukosis/ sarcoma viruses (AL/SV), formerly classified as subgenus avian type C oncornaviruses, are now placed under genus Alpharetrovirus in family Retroviridae (Regenmortel et al., 2005). These include avian leukosis virus (ALV), avian sarcoma virus (ASV) and other ALV-related viruses. These infect large segments of modern poultry industry; hence also present in commercial chickens and eggs, which expose humans on a consistent basis. ALV is type species of the genus (Fadly and Payne, 2003). *Corresponding author : e.mail - alkatomar1@rediffmail.com; alka_tomar@yahoo.com Being retroviruses, AL/SV group of viruses are characterized by possession of reverse transcriptase, which directs synthesis of DNA provirus that gets integrated in the host genome- an essential step during virus replication. These group of viruses have similar physical and molecular characteristics and similar structural polypeptides (p27, p19, p15, p12, and p10) forming nonglycosylated core proteins, also known as group specific antigens (gsag); but different glycosylated envelope (env) proteins, also known as subgroup glycoproteins (sgp) or subgroup specific antigens.

2 232 TOMAR AND SAXENA Based on difference in properties of viral env glycoproteins, AL/SV group of viruses are divided into 10 envelope subgroups, out of this 6 envelope subgroups, viz., A, B, C, D, E and J, infect chickens as natural host (Weiss et al., 1982); and 4 envelope subgroups, viz., F, G, H and I infect pheasants, partridges and quail as natural host (Payne, 1992). Avian leukosis / sarcoma group of infections : Avian leukosis/ sarcoma group of infections include a variety of transmissible benign and malignant neoplastic conditions, non- neoplastic conditions and subclinical infections (Regenmortel et al., 2000). Neoplastic conditions : The neoplastic conditions constitute leukosis/ sarcoma (L/S) group of diseases of chickens. Based on numerous strains of AL/SV, predominant type of neoplasms are induced, viz., lymphoid leukosis (LL) or avian leukosis, erythroid leukosis or erythroblastosis, myeloid leukosis or myeloblastosis, myelocytomatosis, sarcomas, osteopetrosis, hemangiomas, nephroblastomas. Avian leukosis has been the most common disease seen in field flocks; and according to OIE, placed in list C diseases (OIE, 2005). Recently, however, myeloid leukosis has become more prevalent. Non- neoplastic conditions : The non- neoplastic conditions induced by AL/SV include hepatitis, myocarditis, anemia, wasting diseases, arthritis and glomerulonephritis (Crittenden et al., 1982). Subclinical infections : The subclinical infections of AL/SV affect most of the flocks, producing a depressive effect on a number of important performance and fitness traits, viz., reduced egg (25-30 eggs/ hen/ year) and meat production, reduced fertility (2.4%) and hatchability (12.4%) and poor quality of eggs and meat, delayed sexual maturity and nonspecific mortalities in the ALV infected flocks (Gavora, 1987). Transmission of AL/ SV infections : In nature, avian leukosis/sarcoma viruses exist in 2 forms : (1) infectious virus particles, termed exogenous viruses (Fadly and Payne, 2003); and (2) genetically integrated avian retrovirus like elements, termed endogenous viruses (EVs) (Crittenden, 1991) including endogenous viral (ev) loci, moderately repetitive elements termed endogenous avian virus (EAV), avian retrotransposon from chicken genome (ART- CH) and highly repetitive elements termed chicken repeat 1 (CR1). Atleast 29 ev loci have been identified (Gudkov et al., 1986), and each chicken has been reported to carry on average about 5 ev loci (Rovigatti and Astrin, 1983). Exogenous viruses, in infectious state, are transmitted vertically (congenitally) from infected hen to progeny through the egg, and horizontally from bird to bird by direct or indirect contact (Rubin et al.,1962). Though, vertical/congenital route infects only a small percentage of chicks, most chickens become infected horizontally by close contact with congenitally infected birds. The horizontal infection maintains a rate of vertical transmission to prevent AL/SV infection from dying out, maintaining it from one generation to next (Payne and Bumstead, 1982). Hence, congenitally infected chickens remain permanent source of infection at the farm (Payne and Howes, 1991), with high correlation for ALV or gsag shedding in egg albumen, vaginal and cloacal secretions constituting major source of ALV transmission. Endogenous viruses (EV), majorly as noninfectious sequences, are transmitted genetically in Mendelian inheritance pattern from the parent to their progeny, in other words, inherited as host genes by newly hatched chicks (Crittenden, 1991). Endogenous viruses may or may not be expressed and expression may be partial or complete. Partial expression of ev genes can lead to one of the following phenotypes : (1) expression of viral gsag and subgroup E viral env antigen (also known as chicken-helper factor, chf) (gs+ chf+) or; (2) expression of subgroup E viral env antigen (gs- chf+); and (3) complete expression of EV may lead to spontaneous production of infectious subgroup E virus (V-E+); which, in turn, can be transmitted vertically, horizontally or genetically. For eg., ev21 gene is expressed as an infectious endogenous ALV (EV21) in the dam, which is transmitted congenitally to the progeny inducing immunological tolerance and consequently increased susceptibility to infections with exogenous ALV. Though, endogenous viruses have little or no oncogenicity (Smith and Fadly, 1988), they can affect induction of neoplasia and other production or performance traits by their interaction with exogenous ALV; and also directly, if the endogenous viruses are expressed in infectious form. Endogenous AL/SV are believed to be not shed or shed at a very low level, although endogenous AL/SV, other than RAV-0, have been shown to be shed at relatively high levels (Fadly and Payne, 2003). Impact of AL/SV infections : Final outcome of AL/ SV infections will depend on interaction of exogenous

3 SOCIO-ECONOMIC IMPACT OF AVIAN LEUKOSIS/SARCOMA VIRUS INFECTIONS 233 viruses with that of endogenous viruses or their sequences in the chicken host. Thus, presence of ev loci may have either beneficial or detrimental effects due to induction of immunity or tolerance to tumor virus antigens, depending on when they are expressed. For example, ev2 or ev3 protects birds from a unique nonneoplastic syndrome caused by infection with an exogenous subgroup A ALV. Embryonic infection with endogenous ALV caused more persistent viremia and more neoplasms following infection with exogenous ALV, apparently due to tolerant depression of specific humoral immunity. Insertion of ev21 sequence, a locus tightly linked to a dominant sex-linked gene K (regulates slow feathering), into a feather growth locus is responsible for slow feathering mutation. Using feather- sexed crosses, some breeders have reported reduced eggs production and higher leukosis mortality associated with an increased incidence of viremia with exogenous ALV in fast- feathering female progeny from dams carrying K gene. Economic importance of AL/SV infections : Infection of chickens with ALV, the most common AL/ SV infection encountered in field flock, is known to be of significant economic importance. World- over, serious outbreaks of avian leukosis have been reported during the last decade (OIE, 2005). Economic losses from ALV- induced diseases are attributed to 2 sources : (1) tumor mortality, which commonly amounts to around 1-2 % of birds, with occasional losses of upto 20 % or more; and (2) subclinical infections, which affect most of the flocks, producing a depressive effect on a number of important fitness traits, reproductive traits and performance traits, viz., egg and meat production, quality of eggs and meat including egg weight, juvenile bird weight, 6-weeks body weight, delayed onset of sexual maturity and reduced fertility and hatchability (Gavora, 1987; Rout and Pani, 1999), including reduced % hatchability (41-67 %) in guinea chickens and their crosses (Saxena, 1993), reduced number of eggs (68/ hen upto 75 weeks of age), lighter egg weight (2 g) with lower specific gravity (Naithani and Pani, 1999). Shedder hens are characteristically lower, than gsag non- shedding hens, in performance traits and fitness traits. In the reproduction programme, 34% fewer chickens were obtained from ALV shedders, as compared to non- shedders (Ignjatovic et al., 1986). Shedder hens become immunologically tolerant and most likey to develop neoplasms. Economic losses due to ALV tumor mortality and reduced productivity are world- wide, and estimated to be millions of US dollars each year (Chase, 1991). During 1990s, broiler industry identified the ALVinduced myeloid leukosis (Payne, 2000) as its highest disease priority. Losses due to this disease (Spencer et al., 2000) have threatened the economic viability of entire broiler industry. Public health significance Public health significance of AL/SV infections with regard to consumption of chicken origin products: Animal food can be possible source of various human cancers (Willett, 2005; Chao et al., 2005), because it acts as a carrier for various biological agents transmitted from food animals to humans. Cattle, sheep, pigs and poultry provide main source of food for vast majority of mankind, and are naturally infected with plethora of transmissible oncogenic agents, viz., bovine leukemia virus (BLV) in cattle, Jaagsiekte sheep retrovirus (JSRV) in sheep (Buehring et al., 2003; Wootten et al., 2005), pig endogenous retrovirus in pigs (PERV) (Heneine et al., 2001) and avian leukosis/ sarcoma viruses in chickens (Fadly and Payne, 2003). It is interesting that the possible link between occurrence of cancers in general population and transmissible agents originating from animal food would be consistent with the report that dietary sources are the single most important cause of cancer occurrence in humans, possibly accounting for as many as 35 % of all cancers in the US (Doll and Peto, 1981). AL/SV exposure is widespread and virtually universal and occurs on consistent basis in all human populations that consume chickens, eggs and their products. The viruses have been shown to be present in commercial eggs in supermarkets at a prevalence rate of atleast 14 % (Pham et al., 1999), and also in apparently healthy chickens and turkeys and their products destined for human consumption. In one study (Spencer et al., 1977), infectious AL/SV were isolated from 45 % commercial eggs that had been previously stored at 8 0C for 0-6 days, and from 21 % of eggs stored for 7-34 days. Potential human exposure to AL/SV may occur principally in four ways (Johnson, 2005) : (1) exposure of general population through contact with, and /or consumption of chickens and turkeys or their products (including eggs); (2) occupational exposure of persons involved in production, i.e., raising, tending, slaughtering, processing and preparation of chickens

4 234 TOMAR AND SAXENA or their products for food consumption, veterinarians and laboratory workers; (3) exposure of general population from inoculation with vaccines prepared from chicken embryo cells contaminated with these viruses; and (4) potential use of some of these viruses to transport genes into cells or to activate specific host genes in future gene therapy. Recently, two studies have reported presence of antibodies against AL/SV in poultry workers and also in high proportion of subjects in general population with no known occupational exposure to poultry (Johnson et al., 1995; Choudat et al., 1996) indicating widespread exposure to these viruses; although another study did not detect antibodies (Hussain et al., 2001). Experimentally, AL/SV can infect and transform human cells in vitro (Johnson and Griswold, 1996); and can also infect and induce tumors in vivo in mammals including primates (Johnson, 1994). Public Health Significance of AL/SV infections with regard to contamination of chicken origin live virus vaccines of humans and animals : Human vaccines, derived from chicken embryo cultures, are plagued with some very serious viral contamination problems. Evidences clearly suggest presence of particularly ALV viral genomes, reverse transcriptase activity, endogenous retroviruses (ev and EAV elements) as adventitious agents in human vaccines that are prepared in embryonated eggs or in cultures of chicken embryo fibroblasts (CEF), viz., influenza, yellow fever and measles, mumps and rubella (MMR) vaccines (McRearden, 2003). First evidence of contamination of vaccines for human use with AL/SV or its segments came to light in 1960s, when yellow fever vaccine was found to contain ALV (Harris et al., 1966). Since then, it is common knowledge in vaccine industry that these viruses (or its components) still exist in human and animal vaccines (Payne et al., 1966). Virtually, all yellow fever vaccines used during World War II were also contaminated with AL/SV (Waters et al., 1972). In fact, Field's Virology text (2001 Edn.) states, "at the present time, vaccines produced by some of the world's 12 manufacturing institutes are contaminated with avian leukosis virus" (Knipe et al., 2001). A study by the US Centers of Disease Control (US CDC) report that virtually all stocks of measles and mumps vaccine currently in use in United States are contaminated with endogenous form of AL/SV (Tsang et al., 1999). However, reports are contradictory concerning effects of AL/SV or its components on humans in terms of transmission, infection and possible subsequent disease. A study of the US CDC reported no avian viral presence in frozen serum samples from children that had received MMR vaccinations (Hussain et al., 2001); however subsequent reports on exposed poultry workers (Johnson & Griswold, 1996) and workers with no occupational exposure to these viruses (Johnson et al., 1995; Choudat et al., 1996) were reported to have antibodies in their sera specifically directed against AL/ SV. Reports also indicated that given the known behavior of these viruses in mammalian cell culture, a blood serum test would not always provide correct evidence of viral presence in human body. In other words, viruses (or viral antibodies) need not be actively present in blood stream at the time of blood- drawl? It may also be possible that the viral particles may have retreated into other tissues? Exposure of recipients of contaminated vaccines has been associated with effects ranging from benign to demonstrable transmission of infection with or without subsequent diseases. Considering that ALV can easily capture human erbb oncogene; (erbb and myc oncogenes are strongly associated with common form of human breast cancers), it seems that the issue of ALV vaccine contamination would deserve a high level of attention. As is common with other viruses, strains of ALV will show particular affinities for certain type of tissues or growth conditions (Arshad et al., 1997). Further investigations are required whether the virus has been integrated into the human genome to assess public health significance of these results (Johnson et al., 1995). Thus, an accurate assessment of viral presence or long term effects from numerous ALV associated "offspring" virus have yet to be established. In addition, AL/SV is also reported to be potential contaminant of live virus vaccines of poultry. Samples of commercially available Marek's disease (MD) vaccines were found to be positive for both endogenous subgroup E ALV and an exogenous subgroup A ALV, which can cause neoplastic disease and other production problems in susceptible chickens (Silva et al., 2007). Public Health Significance of AL/SV infections with regard to emergence of new viruses from "parent" AL/SV : Avian retroviruses can evolve unexpectedly and pose serious new threats for the poultry industry, human health and animal health. AL/

5 SOCIO-ECONOMIC IMPACT OF AVIAN LEUKOSIS/SARCOMA VIRUS INFECTIONS 235 SV can be considered a "parent" virus, as it easily transforms into a dizzying array of related viruses by transducing one of numerous cancer- related gene segments from its host (including human), and inserting it into its own genome (Felder et al., 1994; Johnson, 1994). It has additional capability of inserting itself into the host (including human) genome as latent virus, and causing cancerous cell transformation from that location. Given right growth conditions, ALV can easily transform into closely related viruses, thus, continuing viral mutations will result in appearance of AL/SV with new disease producing properties. Viruses that originate from the "parent" ALV include potent Rous sarcoma virus (RSV), Rousassociated viruses (RAV), avian myeloblastosis virus (AMV), avian myelocytomatosis virus (AMC), avian erythroblastosis virus (AEV), Fujinami sarcoma virus (FSV) etc., (Nevins, 2001). Serial passaging of a retrovirus (that does not carry an oncogene) on such cultures may lead, with a high frequency, to the emergence of new viruses that have transduced oncogenes. For example, ALV- J strain is thought to be a new strain of virus due to genetic recombinations, possibly among exogenous AL/SV with that of endogenous viruses or even non-retroviral host genes, such as cellular oncogenes. Besides, mutations also occur most frequently in env gene resulting in change in antigenicity and host range manifesting unusual tumors in field. For example, ALV- J strain is a new variant strain of virus causing an unusual tumor, the myeloid leukosis. ALV-J env gene might have arisen by multiple recombination event between one or major EAV family of endogenous virus and exogenous virus. A widespread variant virus of undefined subgroup found in Israel had tropism for endothelial cells and it caused hemangiosarcomas (Burstein et al., 1984). Diagnosis : Diagnosis, based on clinical diseases, represents only 1-20% AL/SV infections, and nearly 80% infections remain undiagnosed, as most AL/SV strains do not produce visible morphologic changes in cell-culture. Hence, most assays for determining presence of exogenous and endogenous AL/SV infections are based on : (1) detection of specific proteins or glycoproteins (gps) coded by 1 or more of 3 major genes of AL/SV, namely gag, pol and env genes or; (2) detection of specific proviral DNA or RNA sequences of AL/SV by polymerase chain reaction (PCR) or reverse transcription (RT)-PCR, respectively. The diagnostic procedures include isolation and identification of the virus, biological, molecular and serological assays. Isolation and identification of AL/SV : Virus isolation is carried out by inoculation of suspected materials in susceptible chicks, embryonated eggs and cell cultures. Rapid transformation of fibroblast cultures is produced only by certain sarcoma viruses and of haemopoitic cell cultures only by certain leukemias viruses (Fadly and Witter, 1998). Biological assays : The biological assays may be direct or indirect. Direct biological assays : Among the structural polypeptides shared by all members of the AL/SV group of avian retroviruses, p27 (major group specific antigen, gsag) is the most abundant. Direct biological assays directly measure p27 either in fluid or in tissue samples by immunological tests e.g., enzyme-linked immunosorbent assay (ELISA), complement fixation (CF) test and radioimmunoassay (RIA); or by immunocytochemical staining procedures e.g., immunofluorescence test (IFT), immunoperoxidase test (IPT), anti- peroxidase assay and protein A-gold assay, respectively. Among all these, ELISA for direct assay of p27 is the most common test used for presence of AL/SV. But, p27 is shared by both exogenous and endogenous viruses; hence direct biological assay can not be used to differentiate between these two groups of viruses. Further, presence of endogenous gsag in chicken tissues limits usefulness of such assays in diagnosing exogenous AL/SVs and for identification of isolated AL/SV (Payne et al., 1993), although in some cases dilution of sample may be helpful to differentiate between endogenous and exogenous AL/ SVs. Currently, ELISA kits for detecting ALV p27 and also for detecting antibody to subgroup A ALV (Smith et al., 1986) are available commercially and are being used extensively by poultry breeders and growers. Monoclonal antibodies (MAbs) against AL/ SV have also been developed and are being used for testing of samples for presence of ALV p27. Recently, MAbs specific for env gp (gp85) of ALV-J was used for detection and identification of ALV-J infected CEF. Most recently, molecularly cloned, baculovirus-expressed env gps of ALV-J is now being used in commercial ELISA kits specific for detection of antibody of ALV-J (Venugopal et al., 1998).

6 236 TOMAR AND SAXENA Indirect biological assays : Indirect biological assays detect presence of exogenous and endogenous AL/ SV infections indirectly employing tests viz., CF for avian leukosis (COFAL) (Sarma et al., 1964), ELISA for ALV (Fadly and Witter, 1998), phenotypic mixing (PM) (Okazaki et al., 1975), resistance inducing factor (RIF) (Rubin, 1960), nonproducer (NP) cell activation assay (Rispens et al., 1970). Of all these, ELISA-ALV is the most common used test. All indirect biological assays require use of chicken embryonic fibroblasts (CEF) with specific host range, such as CEF susceptible to all subgroups of AL/ SV (C/O) or CEF resistant to subgroup E (C/E), subgroup A (C/A) or subgroup J (C/J) etc. A test sample positive for C/O, but negative for C/E indicates presence of endogenous AL/SV. If a sample is positive for both C/O and C/E, it indicates presence of exogenous AL/SV; which can be further subgrouped if the sample is found negative for C/A or C/J, indicating presence of subgroup A or J viruses, respectively. Molecular Assays : Direct molecular assay directly assay 'pol' coded reverse transcriptase (RT), an enzyme essential in multiplication of all retroviruses including ALV (Gallo, 1973). Presently, a highly sensitive PCR-based RT assay has been used to screen human vaccines that are produced in CEF or embryonated eggs for freedom of avian retroviruses (Tsang et al., 1999). An RT-PCR assay has also been developed for subgroup A ALV, alongwith direct sequencing of RT- PCR products, which provides a sensitive technique for differentiating endogenous and exogenous ALV, as also to differentiate viral subgroups of ALV (Pham et al., 1999). Current sequence information of ALV genome (Bai et al., 1995) is being used to design primers for detection of ALV by PCR test. Detection of proviral DNA and viral RNA in various tissues early after ALV infection has also been reported (Van Woenstel et al., 1992). The PCR is the most common DNA-based test used for detection and identification of ALV including subgroup E viruses. Most sequences used for developing primers are located in the env and LTR regions. Several primers specific for the detection of the new subgroup of ALV, ALV-J have recently been developed (Smith et al., 1998; Silva et al., 2007). Primers specific for ALV-J can be used in amplification of DNA isolated from CEFs infected with ALV-J; only culture infected with ALV-J are positive. Other primers specific of ALV-A (Lupiani et al., 2000) can be used in amplification of DNA isolated from CEFs infected with ALV A, only cultures infected with ALV- A are positive. Primers specific for endogenous, subgroup E ALV can also be used to detect CEFs infected with endogenous ALV-E, but not those infected with exogenous ALV of subgroups A, B, C, D and J. Serological assays : Currently, the most specific method for detecting neutralizing antibodies against gp85 envelope antigens of ALV is the virus neutralization test (Mizuno et al., 1970). For detection of antibodies to ALV by virus neutralization tests, reference ALV or RSV stocks, reference antibody to the subgroups A-E of AL/SV, and genetically susceptible CEF culture are required. Antibody to ALV is measured by its reaction with RSV, and the neutralization of virus is determined by reduction in the number of foci induced by RSV (Fadly and Payne, 2003). A microneutralization test using ALV as indicator virus can also be used (Fadly and Witter, 1998). The test can be conducted in 96- well microtitre plates. Neutralization of the virus is determined by an ELISA on culture fluids. Positive ELISA indicates no antibody, whereas a negative ELISA indicates neutralization of ALV and the presence of antibody. Development of an alternate antigen for detection of shedders : Most of the biological assays require virus replication in C/E or C/O fibroblasts and 2-3 weeks cultivation before results are available (Solomon et al., 1971). Even, the most sensitive biological assay available for infectious virus may not identify all the infected dams (Fadly et al., 1981). Molecular assays are costly and unsuitable for field conditions. Therefore, an urgent need is felt for development of an alternate antigen for convenient, precise and early diagnosis of AL/SV infections in chickens under field conditions to determine prevalence of ALV infection in poultry flocks and isolation of ALV subgroup A from chickens with objectives to reduce incidence of ALV infection in general. In this endeavour, Tumor Immunology Laboratory has dedicated for developing an antigen for early and precise diagnosis of AL/SV. Continuous efforts of about a decade have culminated in standardizing procedures for developing a novel antigen. The results obtained so far are encouraging (Tomar,

7 SOCIO-ECONOMIC IMPACT OF AVIAN LEUKOSIS/SARCOMA VIRUS INFECTIONS ; Tomar and Singh, ; Tomar and Singh, ; Anita et al., 2004; Tomar, 2005) Prevention and control strategies : ALVs are still considered ubiquitous in commercial chickens, notwithstanding the eradication programs instituted by many primary breeding companies. With few exceptions, infections occur in all chicken flocks. By sexual maturity, most flocks and most birds within a flock are already exposed. Nevertheless, incidence of subgroup A ALV- induced lymphoid leukosis, the most common neoplasm observed in infected flocks, is usually low (1-2 %), although losses of upto 20 % can occur (Fadly and Payne, 2003). No commercial vaccine is available for protection of chickens from infection with ALV. Use of experimental recombinant AL/SV vaccines may prove to be a valuable adjunct to current programs for reduction or eradication of ALV infection. Recombinant ALVs expressing subgroup A and ALV- J envelope glycoproteins have been produced that could have potential as vaccines to protect against horizontal transmission. Congenitally infected chicks are immunologically tolerant and, thus, can not be immunized, even if a suitable vaccine was available. These chickens constitute major source of ALV transmission and are the most likely to develop neoplasms. Current programs for control of AL/SV infections in chicken breeder flocks are based on selective breeding and elimination of dams that test positive for the virus. Recently, it has been suggested that the unusually high rate of horizontal transmission (Fadly and Smith, 1999) and high frequency of molecular and antigenic variation (Venugopal et al., 1998; Silva et al., 2007) of ALV-J may interfere with success of eradication programs of ALV-J in broiler breeder flocks. Control of AL/SV infection depends mainly on early detection and removal of virus shedding birds to reduce spread of congenital and contact infection in other birds. Programs for eradication of ALV infection depend on breaking vertical transmission of virus from dam to progeny. Application of eradication programs of ALV to commercial flocks depends on association between virus infections in hens, eggs, embryos and chicks. Conclusion : AL/SV infections have been persisting in field as well as in commercial poultry flocks. They cause serious economic losses besides being a threat to human health, with incidence of cancers increasing in human populations. So far, AL/ SV related research has not been paid due attention, therefore, present day need is to strengthen the research efforts to ensure elimination of these infections completely from the poultry flocks to make commercial poultry free of AL/ SV infections. REFERENCES Anita P, Tomar Alka, and Singh B In : XI Con. Of ISVIB and National Symposium, IVRI, Mukteswar (November 3-4, 2004) (Abstract ). Arshad SS, Howes K, Barron GS, Smith LM, Russell PH and Payne LN Vet. Pathol., 34: Bai J, Payne LN and Skinner M J. Virol., 69: Buehring GC, Phillpot SM and Choi KY AIDS Res. Hum. Retroviruses, 19: Burstein H, Gilead M, Bendheim U and Kotler M Avian Pathol., 13: Chase WB In : Proceedings Avian Tumor Virus Symposium, (Eds) D. Swayne and D. Zander, pp 5-7. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Dana Flanders W, Rodriguez C, Sinha R, Calle EE J.A.M.A., 293: Choudat D, Dambrine G, Delemotte B and Coudert F Occup. Environ. Med., 53: Crittenden LB Crit. Rev. Poultry Biol., 3: Crittenden LB, Fadly AM and Smith EJ Avian Dis., 26: Doll R and Peto R J.N.C.I., 66: Fadly AM, Okazaki W, Smith EJ and Crittenden LB Poult. Sci., 60: Fadly AM and Payne LN In : Diseases of Poultry, (Eds) YM Saif, HJ Bernes, JR Glisson, AM Fadly, LR Mcdougald and DE Swayne, 11 th edn., pp , Iowa State Press. Fadly AM and Smith EJ Avian Dis., 43: Fadly AM and Witter RL In : A Laboratory Manual for the Isolation and Identification of Avian Pathogens. (Eds) JR Glisson, DJ Jackwood, JE Pearson, WM Reed and DE Swayne. 4 th edn pp Kennett Square, Pennsylvania : American Assoc. Avian Pathologists. Felder MP, Eychene A, Laugier D, Marx M, Dezelee P and Calothy G Folia Biol. (Praha), 40: Gallo R Nature (London), 234: Gavora JS In : GF de Boer (ed). Avian Leukosis, pp , Martinus Nijhoff, Boston, MA. Gavora J, Spencer J and Chambers J Avian Pathol., 11:

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