Emerging Genotypes of Human Respiratory Syncytial Virus Subgroup A among Patients in Japan

Abstract

Human respiratory syncytial virus (HRSV) is the most common cause of serious acute lower respiratory tract disease among infants and young children, and is found mainly in late fall, winter, and spring in temperate zones of the world (6). Some 50% to 70% of infants experience infection in the first year of life, and virtually all are infected by 2 years of age (3). In a population-based birth cohort study, 1.1% of the cohort were admitted to the hospital within 12 months of birth with HRSV-induced bronchiolitis (14). The consequences of HRSV infection in children with underlying conditions, such as prematurity, cardiac and pulmonary disease, or immunosuppression, may include prolonged substantial illness and even death (18,38). Reinfections are very common throughout life (7,10,11,13).HRSV belongs to the family Paramyxoviridae and has a nonsegmented, negative-sense RNA genome of approximately 15,200 nucleotides (3). HRSV has been classified into antigenic subgroups A and B (HRSV-A and HRSV-B, respectively), initially on the basis of the reactivity of the virus with monoclonal antibodies directed against the attachment glycoprotein (G protein) (1,5,15,21) and now by genetic analyses (9,19,(31)(32)(33).The G protein is the most variable HRSV protein, with two hypervariable regions. Its C-terminal region (the second hypervariable region) accounts for strain-specific epitopes (2-4, 9, 16, 27, 29, 31). The molecular epidemiology and evolutionary patterns of the G protein have provided important information about the epidemiological features of HRSV. Some studies showed that several different genotypes cocirculated and some predominated in a community every year (23, 27). However, the relationship between strain diversity and the clinical and epidemiological features of HRSV has yet to be elucidated in detail.The subgroups have been subdivided further, into genotypes, by genetic analyses. HRSV-A is divided into seven genotypes (GA1 to -7) and HRSV-B into four genotypes (GB1 to -4) (3,8). An additional HRSV-A genotype, SAA1, has been proposed, as well as the new HRSV-B genotypes SAB1 to -3 (37). Another HRSV-B genotype includes the Buenos Aires (BA) type strain, which has a 60-nucleotide insertion in the second hypervariable region of the G protein and has been reported in Buenos Aires in 1999, as well as in other areas of the world (31,35,40). BA strains are further subdivided into six clusters (BA-I to BA-VI) (36).National surveillance of HRSV infection based on weekly reports from sentinel pediatric clinics throughout Japan began

Epidemiology and Diagnosis of Human Respiratory Syncytial Virus Infections

“…Viral nucleotide sequence was identical in several cases. A Japanese study (Shobugawa et al, 2009) investigated a total of 488 human RSV samples from 1,103 screened cases in a pediatric clinic in Niigata. According to the phylogenetic analysis, among the PCR-positive samples, 338 HRSV-A strains clustered into the previously reported genotypes GA5 and GA7 and two novel genotypes, NA1 and NA2, which were genetically close to GA2 strains.…”

Viral/bacterial respiratory tract co-infections in children

“…Co-circulation of multiple subtypes and genotypes has been frequently reported in a single RSV season, although usually one genotype is predominant (189-194, 196-202, 204-209). Within a population the prevalent RSV subtype and genotype has been reported to shift every few years (190,193,194,199,201,205,206,209), most likely due to shortlived, specific herd immunity (210). Genotype replacement has also been observed, where the emergence of a new genotype has appeared to have had a selective advantage, resulting in the replacement of previous lineages by the new genotype in a population (194,205,206,209).…”

“…At least twelve BA sub-genotypes have now been described (194,206,212,213), and they are consistently identified as the predominant RSV-B strains in seasonal epidemics (188, 189, 191-196, 200, 202, 206, 208, 209, 214). In RSV-A, global patterns of RSV epidemics demonstrate that in the mid 1990s genotypes GA2 and GA7 were prevalent, with the emergence of GA5 and the divergence of GA2 into NA1 and NA2 in the 2000s (188,194,201). In 2010, an NA1 variant with a 72 nucleotide duplication in HVR2 was identified in Ontario, Canada (genotype ON1) (203,207).…”

“…However, it has been suggested that successful new genotypes may possess novel antigenicity and thus ability to evade host immunity, resulting in hospitalisation spikes on introduction to a naive population, such as associated with the emergence of ON1, without an inherent ability to cause more severe disease (197,201). This hypothesis is consistent with the increases in hospital and ICU admissions associated with ON1 compared to other RSV strains (197,198), and the large epidemics associated with NA1 and NA2 when they first emerged in Japan in the mid 2000s but not observed since (201 (227). Antibiotic resistance is a growing problem with many bacterial pathogens, and resistance has been observed in S. pneumoniae to both first-and second-line antibiotics commonly used to treat bacterial pneumonia (75)(76)(77)81).…”

“…The ectodomain of G contains two hypervariable regions separated by a putative receptor binding domain that is conserved in both RSV-A and RSV-B. The second C-terminal hypervariable region (HVR2) is sufficient for distinguishing between subtypes and has thus been used by the majority of studies investigating RSV genetic diversity (190,(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204). More recently, whole genome sequencing has also been applied to RSV strains from various clinical settings (188,189,191,192), adding valuable information to our understanding of RSV evolution.…”