Acute hepatitis C in a chronically HIV-infected patient: evolution of different viral genomic regions.
OBJECTIVE
To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.


METHODS
Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.


RESULTS
Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.


CONCLUSIONS
During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattern. Most of the nucleotide substitutions observed are non-synonymous and clustered in previously described epitopes, thus suggesting an immune-driven evolutionary process.
Flichman
Diego
D
Catedra de Virologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Kott
Veronica
V
Sookoian
Silvia
S
Campos
Rodolfo
R
D000208:Acute Disease; D000293:Adolescent; D000595:Amino Acid Sequence; D005260:Female; D016679:Genome, Viral; D006678:HIV / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D015163:Superinfection / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D015699:HIV Envelope Protein gp120; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C400562:HVR1 protein, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase