Absence of nonprimate hepacivirus-related genomes in blood donors seroreactive for hepatitis C virus displaying indeterminate blot patterns.

Despite intensive search, no primate homologue to the Hepatitis C Virus (HCV) has ever been found. The search for a zoonotic origin for HCV has been renewed recently when a virus, now known as non-primate hepacivirus (NPHV), with a high homology to HCV was found in dogs. A variable proportion of anti-HCV reactive blood donors submitted to the immunoblot (IB) to confirm their HCV status, present indeterminate results. The degree of homology between HCV and NPHV suggests that humans may be infected by NPHV or NPHV-like viruses. Maximum similarity between NHPV and HCV is observed in the nonstructural regions 3 and 5. Peptides representing both domains are present in IB assays, so it is reasonable to suppose that blood donors harboring such viruses may display cross-reactivity to the HCV antigenic fractions. Fifty-nine plasma samples from blood donors found reactive for anti-HCV and presenting IB indeterminate results were submitted to five distinct PCR reactions under low-stringency conditions, employing primers targeting GBV-C 5'UTR and NS3, Flavivirus-genus NS5 and NPHV 5'UTR and NS3. No amplification was obtained with all primer pairs tested except for five samples that amplified both 5'UTR and NS3 fragments from GBV-C. Unbiased next-generation sequencing may prove or rule out the existence of HCV-related viruses in IB indeterminate samples.