Increasing genetic diversity of hepatitis C virus in haemophiliacs with human immunodeficiency virus coinfection.
Patients with inherited bleeding disorders who received clotting factor concentrates before 1987 have high rates of hepatitis C virus (HCV) or HCV/human immunodeficiency virus (HIV) infection. To determine whether the persistent nature of HIV affects the genetic diversity of HCV by less selective pressure through the immunosuppression of HIV/HCV-coinfected patients, both the change of genetic diversity and selective pressure were examined in the HCV envelope genes (E1 and E2) of 325 genotype 1a subclones from eight HIV-positive and five HIV-negative patients with two time points (more than 6 years apart). To infer the genetic diversity of HCV in each patient, we used two approaches. One method was to estimate the difference of total evolutionary distances in the phylogenetic tree between the two time points, and another was to estimate the changes of genetic diversity along the time based on the coalescence theory. The two results indicate that the HIV-positive group has significantly more diverse population structure than the HIV-negative group. A comparative analysis of the synonymous and non-synonymous substitutions found that the HIV-positive group was subject to less selective pressure than the HIV-negative group. In conclusion, HIV-positive patients would have a more diversified HCV population than HIV-negative patients due to less selective pressure from the immune system.
Tanaka
Yasuhito
Y
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan.
Hanada
Kousuke
K
National Institute of Genetics, Yata 1111, Mishima, Shizuoka, Japan.
Hanabusa
Hideji
H
Ogikubo hospital, Tokyo, Japan.
Kurbanov
Fuat
F
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan.
Gojobori
Takashi
T
National Institute of Genetics, Yata 1111, Mishima, Shizuoka, Japan.
Mizokami
Masashi
M
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan.
D000328:Adult; D003001:Cloning, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D015658:HIV Infections / Q000150:complications*; D006467:Hemophilia A / Q000150:complications / Q000821:virology*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification
D012367:RNA, Viral