Complementation of the function of glycoprotein H of human herpesvirus 6 variant A by glycoprotein H of variant B in the virus life cycle.
Human herpesvirus 6 (HHV-6) is a T-cell-tropic betaherpesvirus. HHV-6 can be classified into two variants, HHV-6 variant A (HHV-6A) and HHV-6B, based on genetic, antigenic, and cell tropisms, although the homology of their entire genomic sequences is nearly 90%. The HHV-6A glycoprotein complex gH/gL/gQ1/gQ2 is a viral ligand that binds to the cellular receptor human CD46. Because gH has 94.3% amino acid identity between the variants, here we examined whether gH from one variant could complement its loss in the other. Recently, we successfully reconstituted HHV-6A from its cloned genome in a bacterial artificial chromosome (BAC) (rHHV-6ABAC). Using this system, we constructed HHV-6ABAC DNA containing the HHV-6B gH (BgH) gene instead of the HHV-6A gH (AgH) gene in Escherichia coli. Recombinant HHV-6ABAC expressing BgH (rHHV-6ABAC-BgH) was successfully reconstituted. In addition, a monoclonal antibody that blocks HHV-6B but not HHV-6A infection neutralized rHHV-6ABAC-BgH but not rHHV-6ABAC. These results indicate that HHV-6B gH can complement the function of HHV-6A gH in the viral infectious cycle.
Division of Clinical Virology, Kobe University Graduate School of medicine, Kobe, Japan.
Hiroko
H
Oyaizu
Huamin
H
Tang
Megumi
M
Ota
Nobuyuki
N
Takenaka
Keiichi
K
Ozono
Koichi
K
Yamanishi
Yasuko
Y
Mori
D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D022202:Chromosomes, Artificial, Bacterial; D004926:Escherichia coli / Q000235:genetics; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000821:virology; D014759:Viral Envelope Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C070917:glycoprotein H, herpesvirus 6