Molecular epidemiology and clinical characteristics of the human metapneumovirus in South Africa

IV. ABSTRACT The human metapneumovirus is a novel paramyxovirus associated with acute respiratory infections in children, adults, elderly and immunocompromised individuals. It has a worldwide distribution and the prevalence range between 1.5% to 25% in individuals with respiratory infections. Based on phylogenetic analysis 2 distinct genetic groups (A and B) that are sub-divided into four subgroups (A1, A2, B1 and B2) have been shown to circulate. Until recently, there was no information on the molecular epidemiology and the clinical characteristics of the hMPV in Africa, including South Africa, a region with a high prevalence of paediatric human immunodeficiency virus type-1 (HIV) infection. The molecular epidemiology and clinical characteristics of the hMPV in South Africa was investigated over a three period (2000-2002) in children hospitalized with lower respiratory tract infection. The children were part of a cohort participating in a phase 3 clinical trial investigating the efficacy of a 9-valent-pneumocococcal protein-polysaccharide conjugate vaccine (PCV). The objectives of the study were: i. to investigate the molecular epidemiology of hMPV in South Africa; ii. characterize the burden of hMPV disease and determine the clinical features of hMPV-LRTI in children infected and not infected by HIV; iii. probe the role of Streptococcus pneumoniae in the pathogenesis of hMPV-LRTI. The overall prevalence of hMPV in children hospitalized with lower respiratory tract infections (LRTI) was 7.4%. The mean age of children with hMPV associated LRTI (hMPV-LRTI) in South Africa was 13.3 months (range 1.4-49.2 months), with HIV infected children being older than children not infected with HIV (mean [range] 17.6 [4.5-44.3] vs. 12.3 [1.4-49.2] months; P=0.007). The incidence of hMPV-LRTI was 5.0 (95%C.I.3.3-7.5) fold greater in HIV infected children (incidence rate: 2 504 [95%C.I. 1 683-3 577] per 100 000) than in HIV uninfected children (incidence rate: 505 [95%C.I. 409-618] per 100 000, P<0.0001). Human metapneumovirus was identified less frequently than RSV but more commonly than other studied respiratory viruses. The double-blind PCV-9 vs. placebo controlled trial was used to probe the role of pneumococcal co-infections contributing to the pathogenesis of severe hMPV-LRTI. The incidence of hospitalization for hMPV-LRTI was reduced by 46% (95%, CI, 25-63; P=0.0002) in PCV-9 vaccinees compared to placebo recipients. This inferred that coinfection with Streptococcus pneumoniae was integral to the pathogenesis of hMPV-LRTI requiring hospitalization. Both groups of the hMPV circulated during the three year period including concurrent circulation of multiple subtypes of the virus. There was a transition from group B to group A subtype virus as the dominant circulating virus over sequential years. Sequence analysis of the two attachment glycoproteins (F and G), showed the F gene protein to be highly conserved, in contrast the attachment protein gene (G protein) was highly variable particularly in the extracellular domain between lineages. Repeat hMPV-LRTI by either homologous or heterologous strains within 3 months of each other suggested that natural infection did not confer complete immunity to hMPV. The present study demonstrated that hMPV is a leading pathogen associated with LRTI among children in Africa and indicated that occult pneumococcal co-infections’ were integral in the pathogenesis of hMPV-LRTI requiring hospitalization. Additionally, this is the first study to have characterized the molecular epidemiology of hMPV in Africa and provides insight as to issues that may exist regarding the design of an hMPV vaccine

Global Genetic Diversity of Human Metapneumovirus Fusion Gene

We analyzed 64 human metapneumovirus strains from eight countries. Phylogenetic analysis identified two groups (A and B, amino acid identity 93%–96%) and four subgroups. Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age

Mysteries of Type I IFN response: benefits versus detriments

Successful containment of an infection is dependent on both innate and adaptive immune response. Cytokines are essential effectors of both of these systems. In particular, type I interferons (IFN-I) are important components of early innate immunity against an infection. However, the production of IFN-I could serve as a double edge sword, either containing an infection or enhancing susceptibility. For example, IFN-I, which is essential for early containment of viral infections, has been shown to be detrimental to the host during bacterial infections. In fact, recent significant reports have shown that influenza virus induced IFN-I responses can enhance the host susceptibility to secondary bacterial infections. These recent reports highlight the expanding immunoregulatory role of IFN-I in the host immunity. With these recent findings in mind, the aim of this research topic is to welcome novel data, opinion and literature reviews on the newly identified dual functions of IFN-I. This research topic wills focus on the following areas of IFN-I: 1) a detrimental role of IFN-I during primary bacterial infection; 2) a detrimental role of viral infection induced IFN-I during secondary bacterial infections; 3) evolutionary pressure that drove detrimental IFN-I response during primary bacterial infection; and 4) does benefit of IFN-I responses during primary viral infections outweigh the adverse consequences of IFN-I mediated enhanced susceptibility to secondary bacterial infections

Long-term impairment of Streptococcus pneumoniae lung clearance is observed after initial infection with influenza A virus but not human metapneumovirus in mice.

Human metapneumovirus (hMPV) is a paramyxovirus responsible for respiratory tract infections in humans. Our objective was to investigate whether hMPV could predispose to long-term bacterial susceptibility, such as previously observed with influenza viruses. BALB/c mice were infected with hMPV or influenza A and, 14 days following viral infection, challenged with Streptococcus pneumoniae. Only mice previously infected with influenza A demonstrated an 8% weight loss of their body weight 72 h following S. pneumoniae infection, which correlated with an enhanced lung bacterial replication of >7 log(10) compared with pneumococcus infection alone. This enhanced bacterial replication was not related to altered macrophage or neutrophil recruitment or deficient production of critical cytokines. However, bacterial challenge induced the production of gamma interferon in bronchoalveolar lavages of influenza-infected mice, but not in those of hMPV-infected animals. In conclusion, hMPV does not cause long-term impairment of pneumococcus lung clearance, in contrast to influenza A virus.info:eu-repo/semantics/publishe

Human Metapneumovirus Genetic Variability, South Africa

The molecular epidemiology and genetic diversity of the human metapneumovirus (hMPV) were characterized for a 3-year period (2000–2002) from viruses that were identified in South Africa. Two major genetic groups (A and B) and 2 subgroups (1 and 2) of hMPV were identified, as well as 2–6 possible genotypes within the subgroups. A shift in the predominant group was documented in successive seasons. Whereas the F gene was relatively conserved between subgroups, a high degree of variation was observed in the extracellular domain of the G gene of the virus. The G protein identities between groups A and B were 45.1%–53.1% at the nucleotide level and 22.4%–27.6% at the amino acid level. These results provide evidence for the diversity of both surface glycoproteins of hMPV in Africa, which may be a prerequisite to understanding protective immunity against hMPV

No support for an association with TAAR6 and schizophrenia in a linked population of European ancestry

Single nucleotide polymorphisms (SNPs) in the trace amine associated receptor trace amine associated receptor 6 gene and 3\u27 flanking region have been shown to be associated with schizophrenia. To replicate these findings, we conducted a family-based association study with the five most significant SNPs in our sample of 79 sib-pair families (56/79 sib-pair families showed linkage to 6q23) and 125 triads. No evidence for association was obtained between these SNPs and schizophrenia in our sample, even when limited to the 56 linked families (P\u3e0.2). We conclude that trace amine associated receptor 6 is not important for the development of schizophrenia in our family samples