Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection, such as bronchiolitis, bronchitis, or pneumonia, in both infants and the elderly. Despite the global burden of diseases attributable to RSV infection, no clinically approved vaccine is available, and a humanized monoclonal antibody for prophylaxis is not readily affordable in developing countries. There are several hurdles to the successful development of RSV vaccines: immune-vulnerable target populations such as premature infants, pregnant women, and immunocompromised people; safety concerns associated with vaccine-enhanced diseases; repeated infection; and waning memory. To develop successful strategies for the prevention of RSV infection, it is necessary to understand the protective and pathologic roles of host immune responses to RSV infection. In this review, we will summarize the positive and negative relationship between RSV infection and host immunity and discuss strategies for the development of the first successful RSV vaccine.
Humans ; Immunity ; Immunocompromised Host ; Respiratory Syncytial Virus Infections/immunology/*prevention & control ; *Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Viruses/*physiology

The respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and subfamily Pneumovirinae. The RSV can cause acute infections of the lower respiratory tract in infants. The F gene of the RSV is a conservative gene and varies only slightly in its expression. Few studies focusing on the variability of the F gene have been carried out. F protein (fusion glycoprotein) is a transmembrane glycoprotein that mediates fusion and penetration between the virus and host cells. Neutralizing antibody against the F protein can protect against infection by RSV subtypes A and B. Hence, F protein has become the main target for the development of a monoclonal antibody and vaccine against the RSV. An effective vaccine is not available, so a monoclonal antibody against F protein is now the most important method to reduce the morbidity and severity associated with RSV infection in high-risk children. However, a monoclonal antibody can lead to the production of drug-resistant strains of the RSV. This review focuses on genetic variation of the F gene of the RSV as well as progress in the development of a monoclonal antibody against F protein and a vaccine in the last decade.
Animals ; Antibodies, Monoclonal ; immunology ; Humans ; Respiratory Syncytial Virus Infections ; immunology ; prevention & control ; virology ; Respiratory Syncytial Viruses ; genetics ; immunology ; Viral Fusion Proteins ; genetics ; immunology ; Viral Vaccines ; genetics ; immunology

OBJECTIVERespiratory syncytial virus (RSV) is the most common cause of lower respiratory infection in infants. It is very important to quantitative assay of RSV titer in the study on RSV pathogenesis, candidate vaccine and antiviral treatment. Therefore, we develop Real-time Quantitative PCR (Q-PCR) assay and enzyme immunospots (EIS) for titrating RSV and compare them with traditional 50% tissue culture infectious doses (TCID50).

METHODSQ-PCR, based upon the RSV-L genes, and EIS were utilized to titrate samples from RSV culture supernatants and RSV infected mouse lungs. Then, the results were compared with TCID50.

RESULTSFor the samples from RSV culture supernatants, the ratio of Q-PCR and EIS (plaque forming unit, pfu) was 10:1 and the ratio of EIS and TCID50 was 10:1 when TCID50 was converted as pfu. For the samples from RSV infected mouse lungs, the ratio of Q-PCR and EIS was 1000:1 and the ratio of EIS and TCID50 was 5:1.

CONCLUSIONWe have successfully established Q-PCR and EIS to titrate RSV and compared them with TCID50. We concluded EIS is a cost-effective method to titrate RSV.

Cell Line ; Humans ; Immunoenzyme Techniques ; Polymerase Chain Reaction ; Respiratory Syncytial Viruses ; genetics ; immunology

OBJECTIVETo probe the epidemiological trend of respiratory syncytial virus (RSV) and cellular immunological change of RSV bronchopneumonia among children in Suzhou in the past five years.

METHODS10,205 children with acute respiratory tract infection from January 2001 to December 2005 were enrolled into the study. Nasopharyngeal aspirates were obtained from the respiratory tract by aseptic vacuum aspiration. Direct immuno-fluorescence assay was employed to detect seven kinds of virus antigens including RSV antigen. CD3, CD4, CD8, CD19, CD16 and CD56 in peripheral blood mononuclear cells of 30 patients with RSV bronchopneumonia (1.5-24.0 months old group) were analyzed by flow cytometry analysis, and 15 normal infants (1.5-24.0 months old group) were enrolled as control group.

RESULTSThe annual positive rate of RSV was 24.94%, 25.83%, 24.05%, 25.39% and 27.30% respectively from 2001 to 2005. It also found that the peak season for RSV infection was spring or winter (January to March or November to December). The positive rate of RSV was significantly higher in 1-12 months old group than that in > 12 months old group (chi2 = 97.320, P < 0.01), as well as the groups between 1-12 months old (chi2 = 7.804, P < 0.05, the highest positive rate was occurred at 3-6 months old group). The positive rate of RSV was significantly higher in boys than that in girls (chi2 = 9.693, P < 0.01). The percentages of CD3+, CD4+, CD8+ and NK (CD16 + 56)+ cells were significantly lower in RSV bronchopneumonia than those in control group (t = 3.199, P < 0.01; t = 2.215, P < 0.05; t = 2.619, P < 0.05 and t = 5.240, P < 0.01, respectively). While the percentage of CD19+ cells was significantly elevated in RSV bronchopneumonia than that in control group (t = 2.875, P < 0.01).

CONCLUSIONRSV infection is of obvious seasonal changes. The younger the patient, the higher positive rates of RSV infection is, while and the cellular immunity function is lower. The effective measures for preventing RSV infection are important, especially for the infants. Further investigation is necessary to understand the causes of the variations for RSV infections between boys and girls.

Adolescent ; Bronchopneumonia ; epidemiology ; immunology ; virology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Respiratory Syncytial Virus Infections ; epidemiology ; immunology ; Respiratory Syncytial Viruses

OBJECTIVETo investigate the core functional region of antimicrobial peptide LL-37, which inhibites RSV replication and could be developed for theraputic aplication.

METHODSA panel of 6 partial LL-37 peptides (referred to as P1 to P6) was synthesized according to LL-37 amino acide sequence. Hep-2 cells were infected with RSV, treated with LL-37 or partial peptides respectively. Cells were collected after 24 hours incubation at 37 degrees C, CO2 5%. Total RNA was obtained from the cells. Expression level of RSV N gene was quantified by real-time PCR. Meanwhile enzyme-linked immunosorbent assay (ELISA) was used to quantify the chemokines RANTES, IL-8, MCP1 in the supernatants of Hep-2 cultures after 24 h incubation with or without LL-37 and partial peptide P6.

RESULTSN-terminal partial LL-37 peptide (corresponding to residues 1-12 of LL-37) had no significant effects on RSV replication (P > 0.05). In contrast, C-terminal (corresponding to residues 13-37) and a panel of 4 overlapping 22-mer partial peptides (from the peptide incorporating aa 13-34 through that spanning aa 16-37) showed significant inhibitory effect on RSV replication to some extent (P < 0.05 or P < 0.01). LL-37 induced significant expression of chemokine RANTES, IL-8 and MCP-1 in Hep-2 cells. In contrast, partial peptide P6 had no significant effect on expression of the chemokines in Hep-2 cells.

CONCLUSIONThe LL-37 C-terminal 22-mer partial peptide P6 was putative core functional region for inhibition of RSV replication. The partial peptide didn't induce significant expression of chemokine RANTES, IL-8 and MCP-1.

Cathelicidins ; pharmacology ; Cell Line ; Cytokines ; genetics ; immunology ; Humans ; Respiratory Syncytial Virus Infections ; genetics ; immunology ; virology ; Respiratory Syncytial Viruses ; drug effects ; physiology ; Virus Replication ; drug effects

Adenoviridae ; immunology ; Antigens, Viral ; analysis ; Child ; Fluorescent Antibody Technique ; Humans ; Respiratory Syncytial Viruses ; immunology ; Respiratory Tract Infections ; immunology ; Respirovirus ; immunology ; Virus Diseases ; immunology

This investigation enrolled 570 healthy young males gathered from all over the country for military service at the Republic of Korea Air Force boot camp. It confirmed RSV IgG seroprevalence by utilizing the enzyme immunoassay method just prior to undergoing basic training. The mean age of this study was 20.25+/-1.34 yr old. The results of their immunoassay seroprofiles showed that 561 men (98.4%) were positive, 2 (0.4%) were negative and 7 (1.2%) were equivocal belonging to the grey zone. It was confirmed that RSV is a common respiratory virus and RSV infection was encountered by almost all people before reaching adulthood in Korea. Nine basic trainees belonging to the RSV IgG negative and equivocal grey zone categories were prospectively observed for any particular vulnerability to respiratory infection during the training period of two months. However, these nine men completed their basic training without developing any specific respiratory illness.
Adult ; Antibodies, Viral/*blood ; Humans ; Immunoenzyme Techniques ; Immunoglobulin G/*blood ; Male ; Military Personnel ; Respiratory Syncytial Virus Infections/*epidemiology ; Respiratory Syncytial Viruses/*immunology ; Seroepidemiologic Studies ; Young Adult

OBJECTIVETo determine the role of serum leptin in infants with wheezing after respiratory syncytial virus infected.

METHODS43 infants infected with RSV were given blood samples to detect leptin concentration with radioimmunoassays (RIA) within 24 hours after admission into hospital, discharged and 12 weeks later. Then, they were followed up for 2 years. 10 healthy children of the same age served as controls.

RESULTS41.9% infants developed asthma after infected with RSV. Compared to control group, the serum level of leptin in the asthma group and non-asthma group were significantly higher before treatment (t = 3.41 and 2.64 respectively, P < 0.05). When they were discharged, the serum level of leptin in the asthma group was significantly higher than that in non-asthma group and control group (t = 5.74 and 6.23, respectively, P < 0.05). 12 weeks later, the serum level of leptin in the asthma group was still significantly higher than that in non-asthma group and control group (t = 6.32 and 6.11, respectively, P < 0.05), but there were no difference between non-asthma group and control group (t = 0.81, P > 0.05).

CONCLUSIONThe serum level of leptin in infants with asthma after RSV infected was higher than that in healthy and non-asthma children. Persistent higher level of leptin may play an important role in infants with asthma after RSV infected.

Asthma ; blood ; immunology ; virology ; Case-Control Studies ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Leptin ; blood ; immunology ; Male ; Respiratory Sounds ; immunology ; Respiratory Syncytial Virus Infections ; blood ; immunology ; virology ; Respiratory Syncytial Viruses ; immunology ; physiology

AIMTo study the relation between Respiratory Syncytial Virus infection and asthma development by measuring airway responsiveness (AR) and M2R function.

METHODSGuinea pigs (n = 34) were randomly divided into 4 groups: Hep-2/NS group (group A, n = 9), RSV/NS group (group B, n =9), Hep-2/OVA group (group C, n = 8) and RSV/OVA group(group D, n = 8). On day 21 after infection we tested AR and M2R. Then counted eosinophils in BALF and observed pathological change.

RESULTSIntraairway pressure(IP mmH20) of group B had no significant difference with group A(P > 0.01), and the extent of IP decrease also had no difference between groups A and B (P > 0. 05), but IP of C group were much higher than group A (P<0.05), with extent of IP decrease lower than group A (P < 0.05). And IP of group D were higher than group C (P < 0.01), with the extent of IP decrease much lower than group C (P < 0.05).

CONCLUSIONRSV infection could enhance OVA-induced M2R dysfunction, then develop AHR.

Animals ; Asthma ; immunology ; physiopathology ; virology ; Bronchial Hyperreactivity ; immunology ; physiopathology ; virology ; Female ; Guinea Pigs ; Male ; Ovalbumin ; immunology ; Random Allocation ; Receptor, Muscarinic M2 ; physiology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; immunology

OBJECTIVE: To explore the mechanisms for an increase in susceptibility of asthma induced by respiratory syncytial virus (RSV), to observe the expression of interleukin-8 (IL-8) in human bronchial epithelial cells (HBECs) after RSV infection and to invesigate the regulatory effect of IL-8 on Th17/Treg differentiation.
 METHODS: HBECs were divided into a control group and a RSV infected group. The RSVE-infected model of HBECs was established and examined. The expression of IL-8 mRNA was detected by real-time PCR, and the levels of IL-8 were measured by ELISA. Peripheral blood lymphocytes in healthy people were extracted and divided into a control group and an IL-8 treatment group. Based on concentration of IL-8 in RSV-infected HBECs, lymphocytes were treated by a matched concentration of human recombinant IL-8 for 24 h. The distribution of Th17 and Treg subsets in lymphocytes were examined by flow cytometry.
 RESULTS: The RSV-infected HBECs model was successfully established. The infected HBECs were still able to split and passage. The RSV could be detected in every passage in the infected cells. Virus particles indicated by bright yellow green fluorescence were seen under fluorescence microscope. Edema of mitochondrias, expansion of endoplasmic reticulum, fissure around nucleus and intracellular virus particles were all observed under electron microscope. The expression IL-8 mRNA were significantly enhanced in the RSV-infected group, and the level of IL-8 in the RSV-infected group was higher than that in the control group (P<0.05). After IL-8 treatment for 24 h, the ratio of Th17 subsets in lymphocytes were dramatically increased compared to the control group (P<0.05), but there was no difference in the ratio of Treg subsets between the 2 groups (P>0.05).
 CONCLUSION Over-secretion of IL-8 by the RSV-infected HBECs may promote the differentiation of Th17 subsets and maintain the Th17/Tred imbalance.
Cell Differentiation ; Cells, Cultured ; Epithelial Cells ; drug effects ; virology ; Flow Cytometry ; Humans ; Interleukin-8 ; immunology ; pharmacology ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins ; pharmacology ; Respiratory Syncytial Virus Infections ; immunology ; Respiratory Syncytial Viruses ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology