Genetic Variability in the G Protein Gene of Group A and B Respiratory Syncytial Viruses from India

Abstract

Respiratory syncytial virus (RSV) is the most commonly identified viral agent of acute respiratory tract infection (ARIAcute respiratory tract infection (ARI) is the leading killer of children in the world (1.9 million per year), with the greatest number of deaths occurring in developing countries (49). Onefourth (2.5 million) of the total deaths among children less than 5 years of age occur in India (1), and approximately 20% of these are due to ARI (0.5 million) (35,49). Viruses are found in 20 to 40% of children hospitalized with ARIs in India, with respiratory syncytial virus (RSV) being one of the most frequently identified pathogens (15,22,23).RSV strains vary genetically and antigenically and have been classified into two broad groups, groups A and B (2,11,16,25), with additional variability detected within the groups (4, 40). Antigenic variability is thought to contribute to the capacity of the virus to establish reinfections throughout life and may pose a challenge to vaccine design. Future planning for vaccine development will require an understanding of the genetic composition of the RSV strains circulating among target populations.The RSV G protein is a type II integral membrane protein (48) and shows the highest degree of divergence both between and within the two groups (16). The G protein is highly glycosylated, and it is the target for neutralizing and protective immune responses. Variability in the G protein gene is concentrated in the extracellular domain, which consists of two hypervariable regions separated by a central conserved region of 13 amino acids (16). The second variable region, which corresponds to the C-terminal region of the G protein, reflects overall G protein gene variability and has been analyzed in molecular epidemiological studies (5, 33).The objective of the present study was to evaluate the genetic diversity of RSV strains collected in a longitudinal study of ARI from young children in two rural villages in India and from children with ARI seen in an urban hospital. Information about distribution of RSV genotypes in India will be beneficial to the development and implementation of RSV vaccines. MATERIALS AND METHODSClinical samples and diagnosis of RSV infection. The details of this epidemiological study will be described in another report that is under preparation; the results of the molecular epidemiologic study are provided here. Newborns from two rural villages, Nawadha and Mujheri, of Ballabgarh block near Delhi, were enrolled between October 2001 and December 2004 and monitored up to 3 years of age or to the end of the study, March 2005. Two hundred eighty-one children were enrolled, and the total follow-up was 441 child-years. The children enrolled in the study were seen weekly in their homes; approximately 85% of these visits were completed. ARIs were classified according to World Health Organization definitions (50), and nasopharyngeal aspirates (NPAs) were collected at each episode of ARI. ARI was defined as the presence of a cough or difficulty in breathing tha...

Retrospective phylogenetic analysis of circulating BA genotype of human respiratory syncytial virus with 60 bp duplication from New Delhi, India during 2007–2010

“…In addition, the BA viruses have also replaced the existing group B genotypes in different geographical regions [1]. Limited data is available on molecular characterization of BA viruses from India [3,7,15,16]. In the present investigation, we carried out a retrospective molecular and Fig.…”

“…hRSV is major viral pathogen of acute respiratory infection (ARI) in India [3,15,16]. The rapid global spread of the BA genotype suggests that these viruses may have a selective advantage over other hRSV genotypes [21].…”

“…External and semi-nested rounds of PCR for partial G protein gene amplification were carried out with cDNAs using published protocol from our laboratory [15,16].…”

“…Relatively few studies have reported genetic diversity of BA viruses from India [3,7,15,16]. In the present investigation, we have carried out a retrospective molecular and phylogenetic analysis of the circulating strain of the BA genotype from New Delhi, India.…”

Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B

“…However, an improvement to the protective response was not revealed by mixing. The RSV F vaccine was therefore advanced as the preferred vaccine, given that the F gene is better conserved among natural RSV isolates than is G [39][40][41][42]. To determine if that conservation was supportive of cross-neutralization and cross-protection, we tested the rSV-RSV-F construct for elicitation of neutralizing and protective responses against non-homologous challenge viruses.…”