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Simian immunodeficiency virus replicates to high levels in sooty mangabeys without inducing disease
M A Rey-Cuillé1, J L Berthier, M C Bomsel-Demontoy
1Virologie et Immunologie Cellulaire, Institut Pasteur, Paris, France.
Abstract:
A serologic survey of primates living in a French zoo allowed identification of three cases of infection with simian immunodeficiency virus in sooty mangabeys (Cercocebus atys) (SIVsm). Viral isolates, which were designated SIVsmFr66, SIVsmFr74, and SIVsmFr85, were obtained after short-term culture of mangabey lymphoid cells. Phylogenetic analysis of gag and env sequences amplified directly from mangabey tissues showed that the three SIVsmFr were genetically close and that they constituted a new subtype within the diverse SIVsm-SIVmac-human immunodeficiency virus type 2 (HIV-2) group. We could reconstruct the transmission events that likely occurred in 1986 between the three animals and evaluate the divergence of SIVsmFr sequences since transmission. The estimated rate of mutation fixation was 6 x 10(-3) substitutions per site per year, which was as high as the rate found for SIVmac infection in macaques. These data indicated that SIVsmFr replicated at a high rate in mangabeys, despite the nonpathogenic character of infection in this host. The viral load evaluated by competitive PCR reached 20,000 viral DNA copies per 10(6) lymph node cells. In addition, productively infected cells were readily detected in mangabey lymphoid tissues by in situ hybridization. The amounts of viral RNA in plasma ranged from 10(5) to 10(7) copies per ml. The cell-associated and plasma viral loads were as high as those seen in susceptible hosts (humans or macaques) during the asymptomatic stage of HIV or SIVmac infections. Thus, the lack of pathogenicity of SIVsm for its natural host cannot be explained by limited viral replication or by tight containment of viral production.
Insights
Simian immunodeficiency virus (SIVsm) replicates rapidly in sooty mangabeys, a natural host, despite causing no disease. High viral loads in mangabeys challenge explanations for SIVsm
Area of Science:
- Virology
- Primate Immunology
- Molecular Evolution
Background:
- Simian immunodeficiency virus (SIV) is closely related to human immunodeficiency virus (HIV).
- Sooty mangabeys are the natural reservoir for SIVsm, a virus that does not cause disease in its natural host.
- Understanding SIV replication in natural hosts is crucial for insights into HIV pathogenesis.
Purpose of the Study:
- To characterize novel SIVsm isolates from sooty mangabeys in a French zoo.
- To analyze the genetic diversity and evolutionary rate of these SIVsm strains.
- To investigate the viral replication dynamics and pathogenicity in the natural host.
Main Methods:
- Serologic survey of zoo-housed primates.
- Isolation and short-term culture of viral strains from lymphoid cells.
- Phylogenetic analysis of gag and env gene sequences.
- Estimation of mutation fixation rates.
- Quantification of viral load using competitive PCR and in situ hybridization.
Main Results:
- Identification and isolation of three SIVsmFr strains (SIVsmFr66, SIVsmFr74, SIVsmFr85).
- Phylogenetic analysis revealed a new subtype within the SIVsm-SIVmac-HIV-2 group.
- High mutation fixation rate (6 x 10(-3) substitutions/site/year) was estimated.
- Significant viral loads were detected in lymph nodes (20,000 DNA copies/10(6) cells) and plasma (10(5)-10(7) RNA copies/ml).
- Productively infected cells were abundant in lymphoid tissues.
Conclusions:
- SIVsm replicates efficiently in sooty mangabeys, its natural host.
- The lack of pathogenicity is not due to limited viral replication or containment.
- High viral loads in natural hosts are comparable to those in susceptible hosts during asymptomatic infection.
- Further research is needed to elucidate the mechanisms underlying SIVsm non-pathogenicity.