Long-term persistence of HCV lymphotropic variants.

BARÉ PATRICIA; BASTÓN MARIELA; ALOISI NATALIA; CORTI MARCELO; PÉREZ BIANCO RAÚL; DE TEZANOS PINTO M; BRACCO MARÍA MARTA; RUIBAL ARES BEATRIZ

Boston

Congreso; 61st Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2010; 2010

American Association for the Study of Liver Diseases

We aimed to investigate the persistence of HCV genotypes associated to peripheral blood mononuclear cells (PBMC) in chronic carriers. Previous reports documented that a significant proportion of HCV-infected persons can harbor in their PBMC highly divergent viral variants that are not detected in the plasma. Using a non-stimulated cell culture system (J Gen Virol 2005) that allows the detection of HCV genome in culture supernatants (SN), we analyzed the presence over time in 50 hemophiliacs in multiple time points (25 HCV monoinfected and 25 HIV/HCV coinfected) from 1996 up to 2007. HCV genome presence was analyzed by nested-PCR on an average of 15 culture SNs per time point. HCV+ samples were genotyped with restriction fragment length polymorphism and Versant® technique. Serial plasma samples were also studied along the time period and for at least 3 time points per individual. All the HIV/HCV coinfected patients (25/25) and 92% (23/25) of the monoinfected individuals originated HCV+ cultures. We observed that the presence of HCV in PBMC cultures was likely in the setting of HCV+ hemophilic patients. The frequency of HCV+ SN (number of HCV RNA+ SN out of total number of SN examined) ranged from 3 to 79% with a median value of 41.4 and a mean of 38.6 when considering only cultures from patients without HCV treatment. 16 coinfected and 7 monoinfected patients demonstrated the existence of occult HCV mixed-genotype infections in their PBMC with genotypes that did not show in serial plasma samples. Ten coinfected patients showed that multiple HCV genotypes were present in PBMC for 4 to 10 years of infection (see examples in table). Persistence of multiple HCV genotypes in lymphoid cells was proven in the present work. PBMC compartment could act as long term viral reservoir and genotypes of past infections may remain. The clinical and therapeutic implications of lymphotropic HCV variants related to persistence and recurrence requires further investigation, especially in HIV/HCV coinfected persons.