Influence of GBV-C infection on the endogenous activation of the IFN system in HIV-1 co-infected patients.
BACKGROUND
GB virus C (GBV-C) co-infection is associated with a better prognosis in HIV-infected persons. Since interferon activation can be one of the possible mechanisms involved in GBV-C-driven protection against HIV, we compared the endogenous activation of the interferon system in PBMC from GBV-C-positive and -negative patients infected with HIV-1.


METHODS
The expression of interferon related genes was analyzed in 20 GBV-C positive and 20 GBV-C-negative HIV-infected patients, comparable in terms of CD4 cell counts and HIV viral loads. The levels of mRNA for interferon-related genes (2-5-OAS, MxA, interferon AR-1 and PKR) in PBMC were measured by real time RT-PCR, using B-actin as internal control.


RESULTS
The endogenous levels of all the Interferon-related genes in HIV/GBV-C co-infected patients were higher than in HIV mono-infected subjects. The difference was statistically significant for PKR mRNA. Direct positive correlation was found between PKR and all the other interferon-related genes, suggesting a coordinated activation of the interferon system.


CONCLUSIONS
Enhanced activation of the interferon system occurs in GBV-C-positive, as compared to GBV-C-negative patients harbouring HIV-1. These data may be relevant to understand the GBV-C-driven protection against HIV, suggesting that the endogenous activation of the interferon system can contribute to the control of HIV replication.
Capobianchi
M R
MR
Laboratory of Virology. capobianchi@inmi.it
Lalle
E
E
Martini
F
F
Poccia
F
F
D'Offizi
G
G
Antonucci
G
G
Abbate
I
I
Dianzani
F
F
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D018178:Flaviviridae Infections / Q000150:complications* / Q000276:immunology; D029407:GB virus C; D019204:GTP-Binding Proteins / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D015497:HIV-1; D006525:Hepatitis, Viral, Human / Q000150:complications* / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
C579071:MX1 protein, human; D008565:Membrane Proteins; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D007372:Interferons; D019892:eIF-2 Kinase; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins