In humans, HCV clearance is associated with specific IL-28B gene polymorphisms as well as the levels of specific ISG, such as IP-10 
. It has been suggested that these pathways are associated with one another in humans 
although the interrelating mechanism is still unknown. The work presented here was designed to assess whether a potential correlation between IFNλ and polymorphism near the IL-28B gene can be studied in chimpanzees.
In humans, genetic variation near the IL-28B gene is associated with spontaneous as well as treatment-induced clearance of HCV 
. In chimpanzees, we found no evidence for these human SNPs and therefore it is unlikely that these specific SNPs play a role during HCV infection in chimpanzees. Instead, all animals tested were found to be homozygous carriers for rs12979860-TT and rs8099917-TT, which is in line with recently reported data on chimpanzees from another primate center 
. A potential explanation may be that HCV is regarded as a human disease as no documentation is available on wild chimpanzees infected with HCV. In that respect different evolutionary selective pressure may have caused differences in innate responses between both species.
Since the documented SNPs, rs12979860 and rs8099917 are located in an intergenic region rather than within gene-encoding regions of the DNA, there may be a link between the region where the SNPs are located and another, yet unspecified gene. Given the fact that humans and chimpanzees share a common ancestor, the chimpanzee sequence likely represents the ancestral genotypes. This is in line with the finding that Central and Western African human populations carry the rs12979860-TT genotype at high frequency 
Even though humans and chimpanzees show 98.8% identity at the DNA level 
, many SNPs identified in humans are not necessarily present in chimpanzees. Although no evidence was found in chimpanzees for the two SNPs with documented relevance during HCV infection in humans, additional polymorphism near the IL-28B gene was detected. In the animals tested, a remarkable level of heterozygous carriers was observed, which may suggest a balancing selection being operative on this region. Our findings cannot be explained by the breeding strategy as concluded on the basis of variation in the mtDNA 
, and because it was also observed in animals from outside the BPRC breeding colony. The underlying mechanism responsible for this heterogeneity to assure a genetically diverse population is unknown.
In serum from chimpanzees no IFNλ was detected, and therefore no conclusion could be drawn from its effect on the outcome of HCV infection in chimpanzees. IFNλ has been measured in chimpanzees before using human detection reagents 
. Given the rapid normalization of IFNλ levels in chimpanzees shortly after infection, it is expected that IFNλ is too low to detect during the chronic phase of infection. Lower IFNλ levels in chimpanzees could not be explained by a different copy number of the IFNλ-encoding genes as both in humans as well as chimpanzees only one copy of each of the IL-29/IL28A and IL-28B genes was observed (human and chimpanzee database supported by National Institutes of Health, Bethesda, USA).
In patients chronically infected with HCV, low baseline IP-10 levels are predictive for successful treatment-induced clearance 
. Our data show that IP-10 levels are higher in chronically infected chimpanzees relative to patients. This finding is in line with the suggestion that HCV infection causes stronger upregulation of ISGs in chimpanzees as compared to humans 
. Furthermore, based on data from a limited number of animals with high HCV-RNA levels, it was suggested that the failure of chimpanzees to respond successfully to IFN-based antiviral treatment was due to high baseline activation of the IFN-system. Based on our data it is to be expected that peripheral IP-10 levels from the animals in the Lanford-study are high. Given the documented correlation between high IP-10 and limited treatment success in humans, it is tempting to speculate that chimpanzees with a high HCV load and subsequently high baseline IP-10 levels in serum are indeed equivalent to human non-responders to IFN-based therapy. However, this implies that animals with lower IP-10 may respond to IFN-based therapy.
As humans and chimpanzees do not to show the same variation near the IL-28B gene, we were not able to confirm the earlier documented association between IL-28B variation and γGT levels in humans 
. We did however find a correlation between γGT, IP-10 and virus load. This may imply, interrelating mechanisms play a role in both humans and chimpanzees, but that species-specific factors may contribute to biochemical differences between both species.
Our data show that although chimpanzees do not possess the SNP near the IL-28B gene that are associated with HCV outcome in humans, chimpanzees do show genetic variation in this region. Furthermore, we found a positive correlation between IP-10 and viral load as well as γGT in chimpanzees, which was not found in patients. This difference may reflect the heterogeneous characteristics of HCV induced reactions in the liver of both species. The correlation between IP-10, virus load and γGT may reflect the lack of confounding factors in chimpanzees, since heavy alcohol intake, diabetes and obesity are known to influence the progression of HCV infection in humans, but not in chimpanzees.