Vector-borne diseases, such as chikungunya, dengue, malaria, West Nile virus, yellow fever and Zika, pose a major global public health problem worldwide. In this paper we investigate the propagation dynamics of diffusive vector-borne disease models in the whole space, which characterize the spatial expansion of the infected hosts and infected vectors. Due to the lack of monotonicity, the comparison principle cannot be applied directly to this system. We determine the spreading speed and minimal wave speed when the basic reproduction number of the corresponding kinetic system is larger than one. The spreading speed is mainly estimated by the uniform persistence argument and generalized principal eigenvalue. We also show that solutions converge locally uniformly to the positive equilibrium by employing two auxiliary monotone systems. Moreover, it is proven that the spreading speed is the minimal wave speed of travelling wave solutions. In particular, the uniqueness and monotonicity of travelling waves are obtained. When the basic reproduction number of the corresponding kinetic system is not larger than one, it is shown that solutions approach to the disease-free equilibrium uniformly and there is no travelling wave solutions. Finally, numerical simulations are presented to illustrate the analytical results. 
                        more » 
                        « less   
                    
                            
                            Spatial propagation in a within‐host viral infection model
                        
                    
    
            Abstract Recent experimental evidence suggests that spatial heterogeneity plays an important role in within‐host infections caused by different viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). To examine the spatial effects of viral infections, in this paper we study the asymptotic spreading in a within‐host viral infection model, which describes the spatial expansion speeds of viruses and infected cells within an infected host. We first establish the boundedness of solutions to the Cauchy problem via local ‐estimates and dual arguments. Then the spreading speed is estimated when the basic reproduction number of the corresponding kinetic system is larger than one. More precisely, the upper bounds of the spreading speed are given by constructing suitable upper solutions while the lower bounds of the spreading speed are obtained by introducing an auxiliary equation with nonlocal delay. When the basic reproduction number of the corresponding kinetic system is less than or equal to one, the virus dies out uniformly. Finally, we present some numerical simulations to illustrate our theoretical findings and discuss the biological relevance of these results. 
        more » 
        « less   
        
    
    
                            - PAR ID:
- 10445252
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Studies in Applied Mathematics
- Volume:
- 149
- Issue:
- 1
- ISSN:
- 0022-2526
- Format(s):
- Medium: X Size: p. 43-75
- Size(s):
- p. 43-75
- Sponsoring Org:
- National Science Foundation
More Like this
- 
            
- 
            Abstract Despite a vaccine, hepatitis B virus (HBV) remains a world-wide source of infections and deaths. We develop a whole-cell computational platform combining spatial and kinetic models describing the infection cycle of HBV in a hepatocyte host. We simulate key parts of the infection cycle with this whole-cell platform for 10 min of biological time, to predict infection progression, map out virus-host and virus-drug interactions. We find that starting from an established infection, decreasing the copy number of the viral envelope proteins shifts the dominant infection pathway from capsid secretion to re-importing the capsids into the nucleus, resulting in more nuclear-localized viral covalently closed circular DNA (cccDNA) and boosting transcription. This scenario can mimic the consequence of drugs designed to manipulate viral gene expression. Mutating capsid proteins facilitates capsid destabilization and disassembly at nuclear pore complexes, resulting in an increase in cccDNA copy number. However, excessive destabilization leads to premature cytoplasmic disassembly and does not increase the cccDNA counts. Finally, our simulations can predict the best drug dosage and its administration timing to reduce the cccDNA counts. Our adaptable computational platform can be parameterized to study other viruses and identify the most central viral pathways that can be targeted by drugs.more » « less
- 
            null (Ed.)Abstract Although viruses in their natural habitats add up to less than 10% of the biomass, they contribute more than 90% of the genome sequences [1]. These viral sequences or ‘viromes’ encode viruses that populate the Earth’s oceans [2, 3] and terrestrial environments [4, 5], where their infections impact life across diverse ecological niches and scales [6, 7], including humans [8–10]. Most viruses have yet to be isolated and cultured [11–13], and surprisingly few efforts have explored what analysis of available data might reveal about their nature. Here, we compiled and analyzed seven decades of one-step growth and other data for viruses from six major families, including their infections of archaeal, bacterial and eukaryotic hosts [14–191]. We found that the use of host cell biomass for virus production was highest for archaea at 10%, followed by bacteria at 1% and eukarya at 0.01%, highlighting the degree to which viruses of archaea and bacteria exploit their host cells. For individual host cells, the yield of virus progeny spanned a relatively narrow range (10–1000 infectious particles per cell) compared with the million-fold difference in size between the smallest and largest cells. Furthermore, healthy and infected host cells were remarkably similar in the time they needed to multiply themselves or their virus progeny. Specifically, the doubling time of healthy cells and the delay time for virus release from infected cells were not only correlated (r = 0.71, p < 10−10, n = 101); they also spanned the same range from tens of minutes to about a week. These results have implications for better understanding the growth, spread and persistence of viruses in complex natural habitats that abound with diverse hosts, including humans and their associated microbes.more » « less
- 
            Field-grown wheat (Triticum aestivum L.) plants can be co-infected by multiple viruses, including wheat streak mosaic virus (WSMV), Triticum mosaic virus (TriMV), brome mosaic virus (BMV), and barley stripe mosaic virus (BSMV). These viruses belong to four different genera in three different families and are, hence, genetically divergent. However, the impact of potential co-infections with two, three, or all four of them on the viruses themselves, as well as the wheat host, has yet to be examined. This study examined bi-, tri-, and quadripartite interactions among these viruses in wheat for disease development and accumulation of viral genomic RNAs, in comparison with single virus infections. Co-infection of wheat by BMV and BSMV resulted in BMV-like symptoms with a drastic reduction in BSMV genomic RNA copies and coat protein accumulation, suggesting an antagonism-like effect exerted by BMV toward BSMV. However, co-infection of either BMV or BSMV with WSMV or TriMV led to more severe disease than singly infected wheat, but with a decrease or no significant change in the titers of interacting viruses in the presence of BMV or BSMV, respectively. These results were in stark contrast with exacerbated disease phenotype accompanied with enhanced virus titers caused by WSMV and TriMV co-infection. Co-infection of wheat by WSMV, TriMV, and BMV or BSMV resulted in enhanced synergistic disease accompanied with increased accumulation of TriMV and BMV but not WSMV or BSMV. Quadripartite interactions in co-infected wheat by all four viruses resulted in very severe disease synergism, leading to the death of most infected plants, but paradoxically, a drastic reduction in BSMV titer. Our results indicate that interactions among different viruses infecting the same plant host are more complex than previously thought, do not always entail increases in virus titers, and likely involve multiple mechanisms. These findings lay the foundation for additional mechanistic dissections of synergistic interactions among unrelated plant viruses.more » « less
- 
            Lowen, Anice C (Ed.)An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value remains poorly characterized for influenza A virus (IAV), commonly known as the flu. In this study, we screened tens of thousands of cells using a microfluidic method called droplet quantitative PCR (dqPCR). The high-throughput capability of dqPCR enabled the measurement of a large population of infected cells producing progeny virus. By measuring the fully assembled and successfully released viruses from these infected cells, we discover that the viral burst sizes for both the seasonal H3N2 and the 2009 pandemic H1N1 strains vary significantly, with H3N2 ranging from 101to 104viruses per cell, and H1N1 ranging from 101to 103viruses per cell. Some infected cells produce average numbers of new viruses, while others generate extensive number of viruses. In fact, we find that only 10% of the single-cell infections are responsible for creating a significant portion of all the viruses. This small fraction produced approximately 60% of new viruses for H3N2 and 40% for H1N1. On average, each infected cell of the H3N2 flu strain produced 709 new viruses, whereas for H1N1, each infected cell produced 358 viruses. This novel method reveals insights into the flu virus and can lead to improved strategies for managing and preventing the spread of viruses.more » « less
 An official website of the United States government
An official website of the United States government 
				
			 
					 
					
