Influence of specific CD4+ T cells and antibodies on evolution of hypervariable region 1 during acute HCV infection.
OBJECTIVE
Several studies suggest that the evolutionary rate of HVR1 sequence in acute HCV hepatitis derives from the action of a continuous immune-driven positive selection. However, these studies have not been performed examining the relationship between HVR1 evolution and the development of specific immunity to autologous HVR1 sequences.


METHODS
We performed a longitudinal analysis of HVR1 sequences and specific antibodies and CD4+ T cells in ten HCV acutely infected patients with different clinical outcomes (recovery versus persistence).


RESULTS
We showed that although both recovered and chronically evolving individuals developed IFN-gamma+ T cells specific for Core and NS sequences, HVR1-specific CD4+ T cells were detected only in patients clearing the virus. On the contrary, all patients displayed anti-HVR1 antibodies that recognized sequences exclusively carried by autologous viruses. Measurements of genetic diversity and the number of non-synonymous per synonymous substitutions within HVR1 sequences before and after antibody appearance showed an increase of these parameters only in concomitance with the appearance of anti-HVR1 antibodies.


CONCLUSIONS
The evidence that anti-HVR1 antibodies favor HVR1 variant selection suggests that viral complexity in chronically infected patients could represent a virus adaptive strategy to escape the continuous selective process mediated by anti-HVR1 antibodies.
Scottà
Cristiano
C
Department of Cellular and Developmental Biology,"La Sapienza" University of Rome, Italy.
Garbuglia
Anna Rosa
AR
Ruggeri
Lionello
L
Spada
Enea
E
Laurenti
Luca
L
Perrone
Maria Paola
MP
Girelli
Gabriella
G
Mele
Alfonso
A
Capobianchi
Maria Rosaria
MR
Folgori
Antonella
A
Nicosia
Alfredo
A
Del Porto
Paola
P
Piccolella
Enza
E
D000208:Acute Disease; D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
C400562:HVR1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014764:Viral Proteins