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The relationship between the interferon alpha response and viral burden in primary SIV infection
E Khatissian1, M G Tovey, M C Cumont
1Unité d'Oncologie Virale, Institut Pasteur, Paris, France.
Abstract:
The interferon alpha (IFN-alpha) response of rhesus macaques was investigated during primary infection with pathogenic and attenuated simian immunodeficiency virus (SIV). IFN-alpha was detected in the serum of animals as early as day 4 after inoculation of SIVmac251, but remained barely detected in animals infected with the attenuated virus SIVmac251 delta nef. The peak of IFN-alpha secretion preceded that of antigenemia in animals infected with pathogenic virus, indicating that the IFN-alpha response did not prevent viral spread. In addition, elevated levels of IFN-alpha in the serum after the acute stage of infection was associated with persisting antigenemia. The analysis of lymph nodes (LNs) by in situ hybridization showed that, similar to the results obtained with peripheral blood, the induction of IFN-alpha in lymphoid organs was rapidly detected in animals infected with the pathogenic virus, but remained very limited in animals infected with the attenuated virus. Quantitation of the hybridization signal indicated that IFN-alpha-producing cells were numerous in the LNs of animals that had a high viral burden. Taken together, these findings indicate that the IFN-alpha response is unable to contain the initial burst of SIV replication.
Insights
The interferon alpha (IFN-alpha) response in rhesus macaques did not prevent simian immunodeficiency virus (SIV) replication. Elevated IFN-alpha levels correlated with higher viral loads, indicating its inability to control initial SIV infection.
Area of Science:
- Immunology
- Virology
- Primatology
Background:
- The interferon alpha (IFN-alpha) response is a key component of the innate immune system against viral infections.
- Simian immunodeficiency virus (SIV) is a lentivirus that serves as a model for studying human immunodeficiency virus (HIV) pathogenesis.
Purpose of the Study:
- To investigate the role of IFN-alpha in the immune response during primary SIV infection in rhesus macaques.
- To compare the IFN-alpha response to both pathogenic and attenuated SIV strains.
Main Methods:
- Measurement of serum IFN-alpha levels and viral antigenemia in rhesus macaques post-SIV inoculation.
- In situ hybridization analysis of lymph nodes to detect IFN-alpha-producing cells.
- Comparison between animals infected with pathogenic SIVmac251 and attenuated SIVmac251 delta nef.
Main Results:
- IFN-alpha was detected early in pathogenic SIV infection but remained low with attenuated SIV.
- Peak IFN-alpha secretion preceded antigenemia in pathogenic SIV infection, suggesting it did not control viral spread.
- Elevated serum IFN-alpha after the acute phase correlated with persistent antigenemia.
- IFN-alpha-producing cells were abundant in lymph nodes of animals with high viral burdens.
Conclusions:
- The IFN-alpha response in rhesus macaques is insufficient to contain the initial replication burst of pathogenic SIV.
- IFN-alpha induction correlates with viral load, but does not prevent or control SIV pathogenesis.