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1.
PLoS Biol ; 21(7): e3002182, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37410798

RESUMO

The viral hemagglutinins of conventional influenza A viruses (IAVs) bind to sialylated glycans on host cell surfaces for attachment and subsequent infection. In contrast, hemagglutinins of bat-derived IAVs target major histocompatibility complex class II (MHC-II) for cell entry. MHC-II proteins from various vertebrate species can facilitate infection with the bat IAV H18N11. Yet, it has been difficult to biochemically determine the H18:MHC-II binding. Here, we followed a different approach and generated MHC-II chimeras from the human leukocyte antigen DR (HLA-DR), which supports H18-mediated entry, and the nonclassical MHC-II molecule HLA-DM, which does not. In this context, viral entry was supported only by a chimera containing the HLA-DR α1, α2, and ß1 domains. Subsequent modeling of the H18:HLA-DR interaction identified the α2 domain as central for this interaction. Further mutational analyses revealed highly conserved amino acids within loop 4 (N149) and ß-sheet 6 (V190) of the α2 domain as critical for virus entry. This suggests that conserved residues in the α1, α2, and ß1 domains of MHC-II mediate H18-binding and virus propagation. The conservation of MHC-II amino acids, which are critical for H18N11 binding, may explain the broad species specificity of this virus.


Assuntos
Quirópteros , Vírus da Influenza A , Animais , Humanos , Aminoácidos , Antígenos de Histocompatibilidade Classe II , Antígenos HLA-DR/metabolismo , Antígenos HLA
2.
Int J Womens Health ; 7: 75-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25610003

RESUMO

BACKGROUND: Rubella is a contagious viral infection that in pregnant women leads to the infection of a developing fetus, causing fetal death or congenital rubella syndrome. OBJECTIVE: Pregnant women are not routinely screened for rubella in Nigeria. Epidemiological data on rubella is therefore necessary to create awareness and sensitize health care administrators and providers. MATERIALS AND METHODS: A cross-sectional study was carried out at Ahmadu Bello University Teaching Hospital between June and August 2012 to determine the prevalence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to rubella virus in pregnant women using enzyme-linked immunosorbent assay kits. Seroprevalence was compared among 160 pregnant women attending the antenatal clinic of Ahmadu Bello University Teaching Hospital and 20 nonpregnant women of childbearing age studying at Ahmadu Bello University. Prior to sample collection, questionnaires were administered to the women to obtain data on sociodemographics, awareness and knowledge of rubella, possible risk factors, and clinical symptoms associated with the viral infection. RESULTS: Of the 160 pregnant women, 149 (93.1%) and 62 (38.8%) were positive for anti-rubella IgM and IgG antibodies, respectively. Similarly, of the 20 nonpregnant women, 18 (90%) and eight (40%) were positive for rubella IgG and IgM antibodies, respectively. None of the possible risk factors studied were significantly associated with infection. Age and other sociodemographic factors were of little significance, and awareness of rubella was low. CONCLUSION: The prevalence of rubella was high in both pregnant (93.1%) and nonpregnant women (90%), suggesting sustained transmission, which further suggests endemicity. The presence of rubella IgM and IgG antibodies in pregnant women predisposes babies to congenital rubella syndrome and emphasizes the need for the initiation of a national rubella vaccination program in Nigeria.

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