Global distributions and strain diversity of avian infectious bronchitis virus: a review

Abstract The poultry industry faces challenge amidst global food security crisis. Infectious bronchitis is one of the most important viral infections that cause huge economic loss to the poultry industry worldwide. The causative agent, infectious bronchitis virus (IBV) is an RNA virus with great ability for mutation and recombination; thus, capable of generating new virus strains that are difficult to control. There are many IBV strains found worldwide, including the Massachusetts, 4/91, D274, and QX-like strains that can be grouped under the classic or variant serotypes. Currently, information on the epidemiology, strain diversity, and global distribution of IBV has not been comprehensively reported. This review is an update of current knowledge on the distribution, genetic relationship, and diversity of the IBV strains found worldwide.


Introduction
Infectious bronchitis (IB) is a severe and acute disease of poultry caused by the infectious bronchitis virus (IBV). The virus is distributed worldwide and primarily infects the respiratory tract, kidneys, and the reproductive system causing respiratory distress, kidney damage, and decrease in egg production (Cavanagh, 2007). IB was first reported in 1931 and since then it has become a disease that affects the poultry industries in virtually all parts of the world and posing serious challenges to the industry by threatening sustainable poultry farming and the global protein supply. The disease is known to also affect non-domestic galliforms, including exotic and ornamental birds (Liu et al., 2005;Chen et al., 2013).
The emergence of multiple IBV serotypes invariably has hampered control and preventions of the disease. IBV is associated with rapid mutation rates, viral recombination, and host selection pressure. Vaccination has been the most important method for controlling the disease. Live attenuated vaccines are most often used in the vaccination program; however it is plagued with limitations including poor thermostability, reversion to virulence, and recombination between vaccine and field viruses (Tarpey et al., 2006;McKinley et al., 2008;Lee et al., 2010Lee et al., , 2012Bande et al., 2015). These factors may have contributed to the increased emergence of genetically diverse IBV strains that undermines efforts in the control of the disease.

Viral evolution and genotype diversity
There are several widely distributed classic and variant IBV genotypes (de Wit et al., 2011a). Wildtype IBV isolates differ phenotypically from the parental vaccine strain (McKinley et al., 2008;van Santen & Toro 2008;Gallardo et al., 2010). IBV serotypes show variations in approximately 20-25% in their S1 glycoprotein sequences; however the variation can sometimes be as high as 50%, which affects the cross-protection toward virus strains (Cavanagh et al., 1992). As with most of the RNA viruses, changes in IBV often involve the viral genome, leading to generation of several viral genotypes, altered tissue tropism, and infection outcomes (Jia et al., 1995;Lim et al., 2011;Jackwood et al., 2012). Although it is not clearly known how coronaviruses, particularly IBV, evolve, it is postulated that this involves one or more of the following: (i) mutation from nucleotide insertions, deletions, or point mutations as a result of polymerase proof-reading activity; (ii) genomic recombination between vaccines and field strains, leading to multiple template switches as typically observed in the more virulent CK/CH/ 2010/JT-1 IBV isolate that originated from recombination of QX-like, CK/CH/LSC/99I-, tl/CH/LDT3/03-, and 4/ 91-type IBV (Kusters et al., 1990;Rowe et al., 1998;Nix et al., 2000;Zhou et al., 2017). IBV genome analysis showed that regions encoding non-structural proteins 2, 3, and 16, and the S1 glycoprotein have the highest degree of diversity (Thor et al., 2011); and (iii) viral selection pressure that may result from vaccination and presence of partially immune birds.
Changes in tissue tropism has also been reported to cause alterations in the coding sequences of several coronaviruses (Kuo and Masters, 2002;Read et al., 2015). The alteration in the S1 amino acid sequence could occur during adaptation of IBV in Vero cells or following several passaging in chicken embryo (Fang et al., 2005;Ammayappan et al., 2009). Ultimately, viruses that are not 'fit' are eliminated, leaving only 'fit' ones to strive, spread, and cause devastating disease (Zhao et al., 2017).

Pathogenesis and clinical manifestation
Based on tissue tropism, there are two major IBV pathotypes, the respiratory and nephropathogenic pathotypes. Most classic IBV, such as the Massachusetts (Mass) serotype, infects the respiratory tract. However, the nephropathogenic strains, which occurr mostly in Asia and Middle Eastern countries, infect and damage the kidneys. The Moroccan IBV-G reportedly shows tropism for the gastrointestinal tract (GIT). The QX IBV, first isolated in China from the proventriculus (Yudong et al., 1998), are now present in other parts of Asia, Europe, Middle East, and Africa; they show altered tissue tropism, infecting both the kidneys and reproductive tract, causing 'false layers syndrome' and high mortality (Beato et al., 2005;Irvine et al., 2010;de Wit et al., 2011b;Amin et al., 2012;Ganapathy et al., 2012;Naguib et al., 2016).
The upper respiratory tract is the primary replication site for IBV replication and initial infection starts at the epithelium of the Harderian gland, trachea, lungs, and air sacs, then the kidneys, urogenitals, and gastrointestinal tract causing lesions and diseases (Toro et al., 1996;Bande et al., 2016). The replication of IBV pathotypes in the respiratory tract stimulates goblet cell mucus secretion at the mucosal epithelium without causing obvious clinical signs to the birds. However, infected birds may show conditions to include gasping, sneezing tracheal rales, listlessness, and nasal discharges (Britton and Cavanagh, 2008). The QX-like IBV strains infect the kidneys, respiratory, and reproductive tracts, causing severe clinical disease within 48 h of exposure with signs such as frothy-conjunctivitis, profuse lachrymation, edema, and cellulitis of the periorbital tissues. Infected birds become lethargic, reluctant to move, and in some cases, dyspnoeic. The QX strain infects the kidneys and causes wet droppings, excessive water intake, and depression (Terregino et al., 2008;de Wit et al., 2011b). In the reproductive tract, the QX strain may cause generalized lesions in the oviducts, decrease in egg quality, with misshapen rough soft-shelled eggs, and watery egg yolk. The egg production in affected birds declines, but may return to normal following interventions (Winterfield and Hitchner, 1962;Chousalkar et al., 2009;Bande et al., 2016).

Epidemiology and geographical distribution
Some IBV genotypes and serotypes are closely related to the vaccines strains while others are variants that are unique to their geographical regions. In fact, the diversity of IBV in each region should be characterized to determine prevalent strains or genotypes, to improve the efficacy of existing vaccines while developing new ones for control and prevention of the disease.
Recently, a S1-gene-based phylogenetic classification of IBV identified six different viral genotypes, 32 distinct lineages, and several unassigned recombinants with inter-lineage origin. Interestingly, the distribution and diversity of these IBV genotypes differs with geographical location (de Wit et al., 2011a;Valastro et al., 2016). The global distributions of major IBV serotypes such as Mass-type, 4/91 (793B or CR88)-like, D274-like (D207, D212 or D1466, D3896), and D3128, QX-like, and Italy02 are shown in Fig. 1. Some serotypes, for example the QX-like IBV, Mass strain from the USA), 4/91 (CR88) from the UK, and the H120 strains from Netherland are variants causing local and regional impacts but with potentials to spread far and wide to other countries (de Wit et al., 2011a;Jackwood, 2012). For that reason, the QX-based and anti-IBV variants vaccines are being developed to prevent and control the treats of these viruses (Jones et al., 2005;Sasipreeyajan et al., 2012;Kim et al., 2013).

United States of America
In the USA, the first case of IB was reported in early 1930s (Schalk and Hawn, 1931). Since then numerous IBV strains have been identified, of which the Massachusetts or 'Mass' serotype is the most used vaccine serotype. Other IBV strains reported in the USA include the Arkansas, Connecticut, SE17 and Delaware strains (Jackwood et al., 2005). From the IBV field isolates collected in the 1960s, seven isolates belonged to Mass, five were SE17, and one was of the Connecticut (Conn) genotype. This shows that these viruses have long been in existence in this country (Jia et al., 2002;Mondal et al., 2013). The Delaware IBV variant, designated DE072 (Gelb et al., 1997), was first reported in 1992 and found to be distributed across the Northeastern USA. Based on S1 sequence, this variant resembles the Dutch D1466 variant (Lee and Jackwood, 2001). It is not known how the D1466 variant entered the country. The variant was later found to be prevalent in Georgia. The DE072-specific vaccine was then used to control the infection with little or no success. However, use of the DE072 vaccine probably led to the emergence of Georgia 98 (GA98) and GA08 variants (Lee and Jackwood, 2001).

Canada
Characterization of Canadian IBV isolates derived from outbreaks revealed S1 gene sequence with close similarity to the Mass vaccine strains, which include the M41 and Connecticut strains. Two important IBV variants were reported in Ontario, Canada. Of these, the IBV-ON1 variant affects the respiratory system while the IBV-ON4 variant was associated with nephritis. Interestingly, vaccination of chickens with the Mass serotype vaccine protected chickens against challenge with the Ontario IBV strains (Grgić et al., 2008(Grgić et al., , 2009). Later, 9 IBV genotypes were identified and classified into four groups namely; Canadian variant (strain Qu_mv), classic (vaccine-like viruses, Conn and Mass), US variant-like virus strains (California 1734/04, California 99, CU_82792, Pennsylvania 1220/98 and Pennsylvania Wolg/98), and non-Canadian, non-US virus or European strains (4/91 strain) (Martin et al., 2014). The 4/91 strain affected poultry production and there has been a call for the introduction of 4/ 91-specific vaccine to control the infection (Grgić et al., 2008;Martin et al., 2014).

Brazil
The first incidence of IB reported in Brazil was the isolation of Mass IBV serotype (Hipólito, 1957). About 10 years later, the Ark variant emerged, causing devastations to Brazilian poultry (Branden & Da Silva, 1986). Subsequently, 12 new Brazilian isolates were identified based on S1-gene-specific reverse transcriptase polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RLFP). Five of these isolates were the vaccine genotypes of Mass origin, while seven were classified under four Brazilian IBV groups, namely, isolates A (n = 2), B (n = 2), C (n = 2), and D (n = 1). Interestingly, the IBVPR07 isolate, belonging to the Mass serotype, was found to have high tropism for the gonads and trachea (Montassier et al., 2008). Between 2007 and 2008, analysis of positive IB cases among chickens revealed 20 strains, 15 of which were assigned to a major cluster that was sub-classed into the Brazil 01, 02, and 03 isolates. Three isolates were genetically grouped with Mass genotypes while two with the European 4/91 or 793B strain (Villarreal et al., 2007(Villarreal et al., , 2010. In a recent analysis of samples from 63 poultry farms from several regions of Brazil, 11 out of 49 isolates sequenced (22.4%) were of the Mass vaccine strains, 34 (69.4%) are similar to the previously identified and frequently isolated BR-I genotype, and four isolates (8.2%) belong to new IBV variant genotype, Brazil-II or BR-II, which are clearly different from the BR-I genotype. All Brazilian variants from BR-I and BR-II genotypes were characterized by nucleotide sequence insertion coding for five amino acid residues within their S1 glycoprotein. These variants show unique intra-geographic diversity with BR-1 commonly isolated from the South and Southeast regions of Brazil, with the majority of BR-II isolated from the Midwest, and the D207 predominantly in Northeastern parts of Brazil (Fraga et al., 2013). The Brazilian IBV variants, when compared with vaccine genotypes, were found to be >25% divergent, which probably accounts for the low immunogenicity of commercial IBV vaccines (Wei et al., 2008;Chacon et al., 2011).

Argentina
In Argentina, where IB is endemic, vaccination was done with the Mass H120, Ma5 and M41 serotypes. However, sporadic outbreaks still occurred in commercial chicken farms. The likely reason for the vaccine failure was not known until recently, when 20 local IBV isolates from commercial broiler and layer farms were analyzed during the 2001 and 2008 outbreaks. The sequencing and phylogenetic characterization based on the Hyper Variable Regions (HVR) 1 and HVR 1/2 showed that five isolates are of the Mass vaccine genotype, whereas 15 isolates showed unique clustering patterns different from any known vaccine isolates (Rimondi et al., 2009). Amino acid sequence analysis revealed only an average identity of 73.6% between the local variants A, B, and C and the Mass vaccine viruses, which may be the main reason for vaccine failures in this country.

Republic of Chile
Chile had reported cases of IBV infection since 1969 (Garcia and Norambuena, 1969). However, the IBV isolates identified during early outbreaks were serologically classified under the Mass serotype (Hidalgo et al., 1976). Ten years later, a non-Mass IBV serotype was identified to be associated with the frequent vaccination failures (Hidalgo et al., 1986).

Costa Rica
During a 10-week survey in Costa Rica, two new IBV isolates were identified as variant strains. One strain, designated IBV-CR-53, was found to be unique to the country while the other strain was similar to Mass vaccine serotype. Serological evidences of the presence of IBV were obtained from Zenaida asiatica and Columba fasciata pigeons, suggesting that they play a role in the transmission and persistence of IBV in Costa Rica (Lindahl, 2004). Global distribution and diversity of avian infectious bronchitis virus

Cuba
Although IBV has seen in the Caribbean region since the mid-80s (Guilarte, 1985), only recently have novel variants been reported in Cuba (Acevedo et al., 2012). These strains differed genetically from the H120 vaccine serotype that has been approved for use in Cuba. Bioinformatic analysis of the new Cuban isolates, designated Cuba/La Habana/CB6/2009, showed 91.3% nucleotide and 78.3% amino acid sequence identity with the USA/DMV/5642/06 strain that was reported to cause 2006 outbreaks in broilers in Delmarva (Wood et al., 2009). The other Cuban variant, Cuba/La Habana/CB19/2009, presented the highest nucleotide (87.8%), and amino acid (77.4%) sequence identity with B1648, a highly lethal nephropathogenic IBV strain that was first reported in Belgium (Meulemans et al., 2001

Mexico
Mexico has been an important poultry-producing country, which has been plagued with IBV outbreaks. For example, Ark variant, which originated from the USA, was isolated and reported in in the early 1990s (Quiroz et al., 1993). Later, Escorcia et al. (2000) reported four new variants specific to Mexico, as evidenced by RT-PCR and RFLP. Similarly, in 2001 new variants were identified. Of these, Max/1765/99 variant was isolated from 64% of chickens showing respiratory problems; three new isolates were found to be similar with BL-56 earlier reported in 1996, whereas two other indigenous isolates were antigenically similar to Conn genotypes (Gelb et al., 2001).

Africa
In many African countries, the Mass IBV serotypes cause sporadic IB outbreaks in the commercial poultry industry. A number of local variants are reported in Africa in addition to the widely known vaccine serotypes such as Mass and 4/91 strains (de Wit et al., 2011a). In the late 1980s, the IBV-G serotype was identified as a unique African variant with tropism to gastrointestinal system. However, recent studies identified several other local non-vaccine types, including the QX-like strains and Italy 02, originally localized in China and Europe, respectively.

Morocco
The IBV has been present in Morocco since 1989. Five different isolates were identified and designated as D, E, F, H, and M, and classified as the Mass serotypes. However, one isolate, IB-G, was found to be antigenically different from the five isolates and is unique to Morocco. It was later shown that this isolate has tropism for gastrointestinal tissues instead of the respiratory tract. Vaccine efficacy studies showed that immunization of chickens with a Mass-serotype vaccine, such as H120, only protected against challenge with IBV-E and -F and not -G (El-Houadfi et al., 1986;Ambali, 1992). Following an outbreak of IB, where affected birds showed signs typical to that caused by the nephropathogenic strains, Al arabi (2004) conducted RT-PCR and RFLP analyses on several samples from different outbreaks and reported three IBV groups designated I, II and III. Members of group I were classified as the Mass serotype, whereas groups II and III were unique to Morocco. Within the group III types, isolate 12/97 showed high resemblance to previously known enteropathogenic IB-G isolates. This isolate, when experimentally inoculated into chickens, resulted in more severe kidney lesions and higher mortality than the local 7/97 isolate of the same group.
In 2005, five genotypes, three of which differed from the known vaccine strains, and the above viruses were reported to cause serious kidney damage chickens (El Bouqdaoui et al., 2005). More recently, in January 2010 and December 2013, other IBV variants, including the IBV/Morocco/01 IBV/ Morocco/30, and IBV/Morocco/38, were isolated in southern and central regions of Morocco. There were nucleotide sequence identities of 89.5-90.9% between these strains; however, amino acid sequence identities were 29.7% between IBV/Morocco/38 and Egypt SCU-14/2013-1 and 78.2% between IBV/Morocco/ 01 and Spanish Spain/05/866 isolates. Italy 02, a strain that is common in Europe, is the second most common genotype in this country while the 4/91 vaccine strain is diminishing (Dolz et al., 2006(Dolz et al., , 2012Fellahi et al., 2015a, b).

Libya
Information on the prevalence of IBV in Libya is scarce. However, recent studies conducted in Eastern Libya showed the presence of 12 IBV strains that are phylogenetically classified in two distinctive clusters. Isolates from four farms formed a cluster with 94-99% relatedness to the Egyptian IBV strains, CK/Eg/ BSU-2/2011, CK/Eg/BSU-3/2011, and Eg/1212B. Isolates from three other farms were of another cluster that had 100% relatedness to Egyptian Eg/CLEVB-2/IBV/012 and Israeli IS/1494/06 strains (Awad et al., 2014). While the Eg/CLEVB-2/IBV/012 strain was reported to cause respiratory and renal pathology (Abdel-Moneim et al., 2012), the IS/1494/06 strain can cause severe acute renal disorder with morbidity and mortality rates ranging from 15 to 25% (Meir et al., 2004).

Algeria
New IBV genotypes, Algeria28/b1, Algeria28/b2, and Algeria28/b3, were identified in chickens in Algeria. These strains were determined as variants based on the S1 partial sequences. The pathogenic characteristics or immunogenicity of these genotypes have not yet been reported (Sid et al., 2015).

Egypt
Serological evidence of IB was first documented in Egypt in the 1950s (Ahmed, 1954

Ethiopia
Little is known of the epidemiology of IB in East Africa, particularly within the regions of the 'Horn of Africa'. IB was only recently reported to be present in Ethiopia (Hutton et al., 2016) in a study using serology and sequencing approaches to detect IBV isolates from a non-vaccinated institutional farm in Debre Zeit, Ethiopia. The virus was found to be of European 793B genotype, with 92-95% sequence identity with the French isolate, FR-94047-94, and the virulent 4/91 . Because neither the Mass nor 4/91 IBV vaccine is commonly used in African farms, the virus is assumed to be a field isolate.

Nigeria
Although serological evidence for the prevalence of IBV in Eastern Nigeria was shown early in the 1990s (Komolafe There is little information on the pathogenicity or immunogenicity of Nigerian IBV variants, but it is likely that the widely used H120 and M41 vaccines may not protect chickens against these local variants (Ducatez et al., 2009;Valastro et al., 2016).

South Africa
One IBV variant was described in South Africa in 1984; however, this variant has not been fully characterized (Morley and Thomson, 1984). Recently, it was discovered that the Mass IBV serotype is predominant while some QX-like and 793/B genotypes, the CK/ZA/2034/99 and CK/ZA/2281/01, were present in country (Knoetze et al., 2014). The MJT1 and MJT2 variants were reported in non-vaccinated indigenous chickens in the Beitbridge region, bordering Zimbabwe. These chickens presented clinical signs that included dropping of wings, leg paralysis, greenish-watery diarrhea, and respiratory distress. Remarkably, the MJT1 and MJT2 isolates showed 98.6% nucleotide sequence similarity with a QX-like IBV strain, QX L-1148, suggesting that QX-like variants are involved in IB outbreaks South Africa (Toffan et al., 2011(Toffan et al., , 2013.

The Middle East
The prevalence of IBV strains and the disease in the Middle East varied from country to country. A Chinese-like recombinant virus (DY12-2-like) was reported for the first time in the Middle East (Seger et al., 2016 (Shoushtari et al., 2008). The Iranian IRFIBV32 variant, 793/B or CR88-like serotype, has wide tissue distribution, causing marked lesions in the respiratory, urogenital, and digestive systems (Boroomand et al., 2012). These virus strains were also shown to exhibit tropism for the bursa of Fabricius, as observed following inoculation with Iranian IR/773/2001. This suggests that the IRFIBV32 variants have immunosuppressive potential (Mahdavi et al., 2007). The Iranian IBV isolates were also characterized by S1 gene sequencing, and these isolates were then grouped into sixdistinct phylogenetic clusters; namely, IS/1494/06 (Var2)-like, 4/91-like, QX-like, IS/720-like, Mass-like, and IR-1 (3%), with isolation rates of 32, 21, 10, 8, 4, and 3%, respectively (Najafi et al., 2016).

Iraq
The 4/91 IBV serotype is prevalent in Sulaimani, Iraq. There are vaccines available for this and the Ma5 and H120 serotypes. A novel IBV variant, the Sul/01/09, is also prevalent in Iraqi broiler farms, and this variant is distinct from the vaccine and other serotypes reported in Iraq and neighboring countries (Mahmood et al., 2011). More recently, between 2014 and 2015, four major groups were reported in Iraq; namely, group I: variant 2 [IS/1494-like], group II: 793/B-like, group III: QX-like, and group IV: DY12-2-like genotypes. There were 96.42-100, 99.68-100, and 99.36-100% nucleotide sequence identity within groups I, II, and III, respectively. Group I (variant 2) was the most commonly isolated IBV in Iraq.

Jordan
The IBV strains identified in Jordan include Ark, DE-072, and Mass (Gharaibeh, 2007). Other IBV variants later detected were 4/91 and D274; however, two other variants could not be amplified using existing IBV primers (Roussan et al., 2008). Using serotype-specific antisera, antibodies to M41, 4/91 and D274 were detected in clinically healthy flocks (Roussan et al., 2009). Recently, five QX-like IBVs, designated JOA2, JOA4, Saudi Arabia-like [Saudi-1, Saudi-2], and Iraq-like strains were also identified. Phylogenetic analysis showed that the five IBV isolates were 96.6-99.1% related to a Chinese QX-like strain, CK/CH/LDL/97I, and with <80% nucleotide similarity to the M41 and H120 vaccine serotypes. The CK/CH/LDL/97 strain was thought to be associated with sporadic IB outbreaks in the Middle East. It was postulated that the appearance of new IBV strains in Middle Eastern countries is the result of recombination between live attenuated vaccine viruses and field strains (Ababneh et al., 2012).

Israel
In

India, Pakistan, and Bangladesh
There is serological evidence of IBV in Bangladesh (Das et al., 2009), India (Sarma et al., 1984), and Pakistan (Ahmed et al., 2007). In Pakistan, based on antibody titers, the prevalent IBV variants were M41, D-274, D-1466, and 4-91. Recently, a novel nephropathogenic IBV variant, PDRC/Pune/Ind/1/ 00, in Western India was molecularly characterized. This variant was isolated from commercial broiler chickens that manifested clinical signs such as visceral gout and severe nephrosis (Bayry et al., 2005). Although IB vaccines are used in these countries, their effectiveness toward the local strains has not been evaluated (de Wit et al., 2011a).

Australia and New Zealand
Most of the Australian IBV strains are nephropathogenic, and only a few cause respiratory diseases. The nephropathogenic strains were of particular interest as these isolates cause clinical nephritis and mortality in chickens (Ignjatovic et al., 2002).  (Sapats et al., 1996). Recently, a third group was added to the list of prevalent IBV. A representative of the third group, Chicken/ Australia/N2/04, had only a slight homology to the strains from groups 1 and 2. This variant is closely related to the D1466 and DE072 strains from Netherlands and the USA, respectively. Nephropathogenic IBV strains are known as 'T' strains, e.g strains T (N1/62), common to Australia, causes kidney lesions and 5-90% mortality in infected birds (Ignjatovic et al., 2002(Ignjatovic et al., , 2006. Four serologically unique IBV serotypes, A, B, C, and D, were first reported in New Zealand in 1967 (Pohl, 1967;JE. 1988). A vaccine developed against the serotype A was shown to provide protection against all four serotypes, thus has been used to control IB in the country. Recently, T6, K43, and K87 isolates, similar to the strains C and D, and isolate K32, similar to B strain, were identified (McFarlane and Verma, 2008).

Russia and neighboring countries
The Russian IBV isolates are predominantly of the Mass serotypes, although some isolates are related to D274, 4/91, B1648, 624/I, and It-02 genotypes of European origin. Two novel QX-like isolates were reported in regions bordering Russia, the Far East and Europe. Among these isolates, 27 are unique Russian variants, distinct from known IBV strains (Bochkov et al., 2006). An extensive epidemiological study on IB in this region that included Russia, Ukraine andKazakhstan, between 2007 and, showed the dynamics of IBV has changed with the Mass, 793/B, D274 and QX-like IBV, now becoming the most prevalent genotypes, followed by the B1648, Italy-02, and Arkansas variants. Eleven 4/91-related IBV isolates were reported, which included recombinants of the field and vaccine strains and the local strains designated UKR/02/2009 (or 4/91), RF/03/2010, and RF/01/2010 (Ovchinnikova et al., 2011).
A study that determined IBV variants in Western Europe showed that 793B serotype was predominant, followed by Mass type, H120, M41, IBM, Italy02, and a variant closely related to the Chinese QX isolate (Worthington et al., 2008). It is important to note that QX-like IBV, which was first isolated in Europe in 2004, has recently emerged as the most challenging IBV in Europe. Although, in China, this isolate was initially known to cause mild proventriculitis (Yudong et al., 1998), in Europe its tropism had changed to the kidneys and oviduct (Monne et al., 2008). QX-like IBV serotypes have been reported in Scotland (Worthington et al., 2008), Italy (Beato et al., 2005), The Netherlands, Poland (Domańska-Blicharz et al., 2007), Slovenia (Krapez et al., 2011), Spain, UK (Valastro et al., 2010;Ganapathy et al., 2012), and Sweden (Abro et al., 2012). Similarly, QX, D274-like and 4/91-like IBV serotypes have recently been reported in Finland where the use of live IBV vaccines is not practiced (Pohjola et al., 2014).

Asia
It has been speculated that the IBV strains have long been in existence in Asia. This speculation is based on the phylogenetic diversity of various isolates found the region (Yu et al., 2001).
Among these countries, China has experienced the emergence of several distinct IBV variants. The QX strain, in particular, has spread to other parts of the world to include Europe, the Middle East and Africa. This strain is the result of remarkable change in the genetics of IBV, and currently there is no effective vaccine available to control the infection by this virus variant (W Yudong et al., 1998;Worthington et al., 2008).

Malaysia and Singapore
Malaysia first documented cases of IBV infection in 1967. Most IBV isolated before the 1990s were antigenically similar to the vaccine strain viruses of the Mass serotype (Arshad, 1993). Subsequent studies identified two unique IBV variants, the nephropathogenic variant, MH5365/95, and the respiratory pathogenic strain, V9/04, isolated in 1995 and 2004, respectively. These variants were later shown to have remarkable similarity with several Chinese isolates (Zulperi et al., 2009).
Singapore also suffered from IB infections. Most serotypes identified, based on their antigenic relatedness, were classified under Mass-like serotype (Yu et al., 2001).

Thailand
Outbreaks of IBV infection began to occur in Thailand in the early 1960s (Chindavanig, 1962). Sequence analysis of 13 samples isolated in 2008 in Thailand revealed two IBV groups. Group 1 isolates, THA20151, THA40151, THA50151, and THA60151, were unique to Thailand, and group 2 isolates, THA30151, THA 70151, THA 80151, THA100151, THA110351, THA120351, THA130551, and THA140551, had 97-98% and 96-98% nucleotide and amino acid sequence identities, respectively, with the QX A2, SH and QXIBV serotypes that are endemic in China. An attenuated vaccine was developed from the Thailand QX-like THA80151IBV isolate, which was shown to prevent clinical disease despite evidence of viral replication and pathologic lesions in the trachea and kidneys (Sasipreeyajan et al., 2012).

Indonesia
In Indonesia, IBV was first described in the 1970s (Ronohardjo, 1977). Based on antigenic characteristics, an Indonesian isolate, I-37, cross-reacted with the Conn 46 strain of US origin; three isolates, I-269, I-624, and PTS-II, cross-reacted with the Mass 41 vaccine strain, while two isolates, I-625 and PTS-III, were related to Australian N2/62 strain (Darminto, 1995;Indriani, 2000). Further analysis of the I-37 isolate showed differences of approximately 6.9 and 15.6% in nucleotide and amino acid sequences, respectively, with the Conn-46 isolate. Thus, I-37 was suggested to be a variant of Conn 46 serotype, probably arising from vaccine-virus recombination events. Whether there are any functional and/or genomic differences between the two isolates is yet to be determined (Dharmayanti et al., 2005).

South Korea
Most IBV variants in South Korea are of nephropathogenic pathotypes, classified either as KM91-like, QX-like, or recombination strain (Song et al., 1998;Jang et al., 2007;Lim et al., 2011). A recent analysis of 27 IBV variants isolated from 1990 to 2011 classified the Korean IBV isolates into five genotypes: (i) Mass vaccine serotype, (ii) Korean-I (K-I), (iii) Chinese QX-strain-related, (iv) KM91-like isolates, and (v) isolates that do not fit into any known group of Korean strains. Two genotypes, 11036 and 11052, appeared to be generated from recombination events between the new Korean genotype in cluster 1 and Chinese QX-like strain and between K-I and H120-vaccine serotype, respectively .

Japan
In Japan, variant IBV co-exists with Grey and Mass isolates (Mase et al., 2004). Local variants have shown a different clustering pattern from existing isolates but are closely related to isolates from China and Taiwan

China
In China, IBV was first reported in the mid-1980s. To control IBV infection in chickens in this country, the live attenuated and killed-oil adjuvant vaccines, derived from Mass (H120 and Ma5) and Conn serotypes, were used. However, these vaccines only served to reduce, not eradicate, the problem, because the disease continued to remain a major treat to the poultry industry (Han et al., 2011). IBV in China showed great diversity, although several Mass and 4/91-like isolates were reported in the country (Liu and Kong, 2004;Xie et al., 2011;Ma et al., 2012). The QX and LX-like IBV strains were also isolated, which are distinct from known vaccine serotypes (Yudong et al., 1998;Zhao et al., 2017) and these strains are broadly classified as A2-like and QX-IBV strains (Xu et al., 2007;Zou et al., 2010;Li et al., 2013).

Taiwan
In Taiwan, IBVs were first described in the early 1960s with isolates of the Mass vaccine serotypes. Most local IBV variants are grouped together with the Chinese strains (Huang and Wang, 2006). A Taiwanese IBV strain, designated Taiwan II, is closely related to TW2296/95 serotype, which was also isolated in mainland China .

Conclusion
It is evident that IBV has become endemic worldwide. It is of great concern to the poultry industry that new IBV variants are persistently emerging. These new virus variants do not respond to existing vaccines currently in use. Although some genotypes are restricted to certain geographic regions, others such as Mass, IBV 4/91 (CR88 or 7/91B) and the recently emerging QX-like IBV are more global in distribution. As such, these global genotypes can be considered for the development of novel multivalent universal vaccines. However, a regional vaccination strategy based on specific local strains can be adapted in addition to the general vaccines based on the ubiquitous genotypes.