Infectious diseases can seriously impact dynamics of their host species. In this study, we model and analyze an interaction between a sexually transmitted infection and its animal host population affected by a mate-finding Allee effect. Since mating drives both host reproduction and infection transmission, the Allee effect shapes the transmission rate of the infection which we show takes a saturating form. Our model combining sexually transmitted infections with the mate-finding Allee effect in the host produces quite rich dynamics, including oscillations, several multistability regimes, and infection-induced host extinction. However, many of these complex patterns are restricted to a relatively narrow parameter range. We find that the host extinction occurs at intermediate levels of infection virulence, as well as for Allee effect strengths much lower than when the infection is absent. In both cases, a sequence of events comprising destabilization of an endemic equilibrium, growth of oscillation amplitude, and a heteroclinic bifurcation forms an underlying mechanism. We apply our model to the feline immunodeficiency virus (FIV) in domestic cats.
- MeSH
- biologické modely * MeSH
- hustota populace MeSH
- infekční nemoci MeSH
- interakce hostitele a patogenu * MeSH
- kočičí AIDS přenos virologie MeSH
- kočky MeSH
- populační dynamika MeSH
- populační růst MeSH
- sexuálně přenosné nemoci MeSH
- virus kočičí imunodeficience * MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Infection with feline immunodeficiency virus (FIV) causes an immunosuppressive disease whose consequences are less severe if cats are co-infected with an attenuated FIV strain (PLV). We use virus diversity measurements, which reflect replication ability and the virus response to various conditions, to test whether diversity of virulent FIV in lymphoid tissues is altered in the presence of PLV. Our data consisted of the 3' half of the FIV genome from three tissues of animals infected with FIV alone, or with FIV and PLV, sequenced by 454 technology. RESULTS: Since rare variants dominate virus populations, we had to carefully distinguish sequence variation from errors due to experimental protocols and sequencing. We considered an exponential-normal convolution model used for background correction of microarray data, and modified it to formulate an error correction approach for minor allele frequencies derived from high-throughput sequencing. Similar to accounting for over-dispersion in counts, this accounts for error-inflated variability in frequencies - and quite effectively reproduces empirically observed distributions. After obtaining error-corrected minor allele frequencies, we applied ANalysis Of VAriance (ANOVA) based on a linear mixed model and found that conserved sites and transition frequencies in FIV genes differ among tissues of dual and single infected cats. Furthermore, analysis of minor allele frequencies at individual FIV genome sites revealed 242 sites significantly affected by infection status (dual vs. single) or infection status by tissue interaction. All together, our results demonstrated a decrease in FIV diversity in bone marrow in the presence of PLV. Importantly, these effects were weakened or undetectable when error correction was performed with other approaches (thresholding of minor allele frequencies; probabilistic clustering of reads). We also queried the data for cytidine deaminase activity on the viral genome, which causes an asymmetric increase in G to A substitutions, but found no evidence for this host defense strategy. CONCLUSIONS: Our error correction approach for minor allele frequencies (more sensitive and computationally efficient than other algorithms) and our statistical treatment of variation (ANOVA) were critical for effective use of high-throughput sequencing data in understanding viral diversity. We found that co-infection with PLV shifts FIV diversity from bone marrow to lymph node and spleen.
- MeSH
- algoritmy MeSH
- DNA virů genetika MeSH
- interpretace statistických dat * MeSH
- kočičí AIDS genetika imunologie virologie MeSH
- kočky MeSH
- nemoci koček genetika imunologie přenos virologie MeSH
- statistické modely * MeSH
- virus kočičí imunodeficience klasifikace genetika patogenita MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH