一类CD4＋T细胞感染HIV病毒模型的全局稳定性

研究了一类具有标准发生率的CD4＋T细胞感染HIV病毒模型的动力学性质．通过分析,得到了病毒消除与否的阚值一基本再生数．证明了当基本再生数小于1时,未感染病毒平衡点全局渐近稳定,病毒将在宿主体内被清除．当基本再生数大于1时,病毒将在宿主体内持续生存,进一步给出了病毒感染平衡点全局渐近稳定的条件．最后对所得结论进行了数值模拟．     

一类具有治愈率的HBV病毒感染模型的全局稳定性

本文研究了一类具有治愈率的HBV病毒感染模型的动力学性质.通过分析,证明了当基本再生数小于1时,未感染病毒平衡点全局渐近稳定,病毒在宿主体内被清除.当基本再生数大于1时,病毒在宿主体内持续生存,同时给出了病毒感染平衡点全局渐近稳定和存在轨道稳定周期解的充分条件.     

一类具有CTL作用的HIV感染模型的全局稳定性

通过假设无HIV感染时个体体内的CTL细胞存在常数输入和被感染CD4+T细胞对CTL细胞繁殖的影响具有饱和形式,本文建立了一类具有CTL作用的HIV感染模型,得到了确定模型动力学性态的基本再生数.当基本再生数不大于1时,健康平衡点在可行域上是全局渐近稳定的,即HIV在个体体内最终灭绝;当基本再生数大于1时,模型的惟一感染平衡点在可行域内是全局渐近稳定的,即HIV将在个体体内持续存在,并且其浓度最终趋于一个正常数.     

具有Crowley-Martin功能反应和CTL免疫反应的病毒动力学模型的全局稳定性（英文）

本文讨论了一类具有Growley-Martin功能反应和CTL免疫反应的病毒动力学模型的全局稳定性.利用Lyapunov函数和LaSalle不变原理证明:当基本再生数R_0≤1时,无病平衡点全局渐近稳定;当基本再生数R_01且免疫基本再生数R_0≤1时,免疫平衡点全局渐近稳定;当R_01时,地方病平衡点全局渐近稳定.     

具有时变接触率与接种率的脉冲传染病模型研究

讨论了时变接触率和时变接种率的传染病模型,模型中考虑对易感者和染病者同时接种.通过计算得到了判别疾病流行与否的阈值.证明了当基本再生数小于1时,疾病是流行的;当基本再生数大于1时,疾病将成为地方病.     

具有潜伏和隔离的传染病模型的全局稳定性

研究了一类具有隔离仓室和潜伏仓室的非线性高维自治微分系统SEQIJR传染病模型,得到疾病绝灭与否的阀值一基本再生数R0．证明了当R0≤1时,模型仅存在无病平衡点,且无病平衡点是全局渐近稳定的,疾病最终绝灭;当R0〉1时,模型存在两个平衡点,无病平衡点不稳定,地方病平衡点全局渐近稳定,疾病将持续．隔离措施影响着基本再生数,进而推得结论：适当地增大隔离强度,将有益于有效地控制疾病的蔓延．这就从理论上揭示了隔离对疾病控制的积极作用．     

一个带有ATL过程的HTL V-I感染的时滞模型

本文提出并分析了两个关于人体T-细胞淋巴回归Ⅰ型病毒（HTL V-I）感染并带有坏死白血病细胞（ATL）进程的数学模型,一个常微分方程模型,一个离散时滞模型.首先对常微分方程模型进行了分析,运用相应的特征方程得到一个阈值Ro（CD4⁺ T-细胞的基本再生数）.当R₀≤1时,仅有未染病平衡态存在,并且给出了其稳定性;当R₀>1时,有一个染病稳定态存在,并且此时它是稳定的.然后,我们在常微分方程模型中引入了一个离散时滞,通过对时滞模型的超越特征方程的分析,导出了与常微分方程模型中同样的稳定性条件,即时滞模型平衡态的稳定性与时滞的具体值无关.     

具有连续接种和脉冲接种的SIVR模型研究

考虑了具有连续接种和脉冲接种的SIVR传染病模型,得到了模型的基本再生数.对于连续接种模型,证明了当基本再生数R_0~c≤1时无病平衡点是全局稳定的;当R_0~c1时,无病平衡点是不稳定的,模型存在地方病平衡点,并且当δ=0时,地方病平衡点是全局渐近稳定的.对于脉冲接种模型,得到了无病周期解的存在性和稳定性.最后,对连续接种和脉冲接种进行了比较.     

一类随机SIR流行病模型的渐近行为研究

考虑了一类恢复率受到噪声影响的随机SIR流行病模型.首先证明了模型非负解的全局存在惟一性;其次证明了当基本再生数R₀≤1时无病平衡点随机渐近稳定,当R₀>1时随机模型的解围绕确定性模型地方病平衡点震荡.最后通过数值仿真验证了所得结论的正确性.     

一类基于边的随机SEIR网络模型的传播动力学

考虑到疾病传播的异质性,本文基于配置模型建立了一类基于边的随机SEIR网络传播动力学模型.数值仿真显示网络随机模拟结果与所建模型的解能够很好地吻合.得到了疾病流行的基本再生数,并证明了疾病在网络上能否流行由其基本再生数唯一决定:当基本再生数不大于1时,模型存在唯一稳定的相应于疾病在网络上没有流行开来的平衡点;当基本再生数大于1时,疾病未流行平衡点变为不稳定,此时模型存在另一个稳定的相应于疾病在网络上流行开来的平衡点.     

A chronic viral infection model with immune impairment

In this paper, a chronic viral infection model with cell-mediated immunity and immune impairment is proposed and studied, under the assumption that the presence of the antigen can both stimulate and impair immunity. It is shown that the virus persists in the host if the basic reproductive ratio of the virus is greater than 1. The immune cells persist when there is only one positive equilibrium. The system can exhibit two positive equilibria if the basic reproductive ratio of the virus is above a threshold. This allows a bistable behavior, and the immune cells persist or die out, i.e., infection will result in disease or immune control outcome, depending on the initial conditions. By theoretical analysis and numerical simulations, we show that therapy could shift the patient from a disease progression to an immune control outcome, despite that the therapy is not necessarily lifelong. This would allow the immune response to control the virus in the long term even in the absence of continued therapy.     

Optimal viral production

Viruses reproduce by multiplying within host cells. The reproductive fitness of a virus is proportional to the number of offspring it can produce during the lifetime of the cell it infects. If viral production rates are independent of cell death rate, then one expects natural selection will favor viruses that maximize their production rates. However, if increases in the viral production rate lead to an increase in the cell death rate, then the viral production rate that maximizes fitness may be less than the maximum. Here we pose the question of how fast should a virus replicate in order to maximize the number of progeny virions that it produces. We present a general mathematical framework for studying problems of this type, which may be adapted to many host-parasite systems, and use it to examine the optimal virus production scheduling problem from the perspective of the virus.     

Screening of a High Growth Influenza B Virus Strain in Vero Cells

Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus.The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines.However,most of the influenza viruses can not grow well in Vero cells.To develop a new influenza vaccine with Vero cells as a substrate,the virus needs to adapt to th...     

Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus.

An animal model for the heterosexual transmission of human immunodeficiency virus (HIV) was developed by the application of simian immunodeficiency virus (SIV) onto the genital mucosas of both mature and immature, male and female rhesus macaques. Virus preparations were infused into the vaginal vaults or the urethras (males) of the animals through a soft plastic pediatric nasogastric feeding tube. The macaques that were infected by this route (six males and nine females) developed SIV-specific antibodies, and SIV was isolated from peripheral mononuclear cells of all seropositive animals. One male and one female infected by this route developed severe acquired immunodeficiency syndrome-like disease with retroviral giant-cell pneumonia. As few as two inoculations of cell-free SIV containing 50 50% tissue culture infective doses induced persistent viremia. Cell-free virus preparations were capable of producing infection by the genital route. Much higher doses of virus were required to transmit SIV by this route than are required for transmission by intravenous inoculation. Thus, it appears that the mucous membranes of the genital tract act as a barrier to SIV infection. Spermatozoa and seminal plasma were not required for the genital transmission of SIV. Rarely, SIV was recovered from mononuclear cells in semen and vaginal secretions. The SIV-rhesus macaque model is suitable for assessing the role of cofactors in heterosexual transmission of HIV and will be useful for testing the effectiveness of spermicides, pharmacologic agents, and vaccines in preventing the heterosexual transmission of HIV.     

Increased burst size in multiply infected cells can alter basic virus dynamics

ABSTRACT: BACKGROUND: The dynamics of viral infections have been studied extensively in a variety of settings, both experimentally and with mathematical models. The majori-ty of mathematical models assumes that only one virus can infect a given cell at a time. It is, however, clear that especially in the context of high viral load, cells can become infected with multiple copies of a virus, a process called coinfection. This has been best demonstrated experimentally for human immunodeficiency virus (HIV), although it is thought to be equally relevant for a number of other viral infections. In a previously explored mathematical model, the viral output from an infected cell does not depend on the number of viruses that reside in the cell, i.e. viral replication is limited by cellular rather than viral factors. In this case, basic virus dynamics properties are not altered by coinfection. Results: Here, we explore the alternative assumption that multiply infected cells are characterized by an increased burst size and find that this can fundamentally alter model predictions. Under this scenario, establishment of infection may not be solely determined by the basic reproductive ratio of the virus, but can depend on the initial virus load. Upon infection, the virus population need not follow straight exponential growth. Instead, the exponential rate of growth can increase over time as virus load becomes larger. Moreover, the model suggests that the ability of anti-viral drugs to suppress the virus population can depend on the virus load upon initiation of therapy. This is because more coinfected cells, which produce more virus, are present at higher virus loads. Hence, the degree of drug resistance is not only determined by the viral genotype, but also by the prevalence of coinfected cells. Conclusions: Our work shows how an increased burst size in multiply infected cells can alter basic infection dynamics. This forms the basis for future experimental testing of model assumptions and predictions that can distinguish between the different scenarios.     

An endoplasmic reticulum-retained herpes simplex virus glycoprotein H is absent from secreted virions: evidence for reenvelopment during egress.

Although it is generally accepted that one of the first steps of herpesvirus egress is the acquisition of an envelope by nucleocapsids budding into the inner nuclear membrane, later events in the pathway are not well understood. We tested the hypothesis that the virus then undergoes de-envelopment, followed by reenvelopment at membranes outside the endoplasmic reticulum (ER), by constructing a recombinant virus in which the expression of an essential glycoprotein, gH, is restricted to the inner nuclear membrane-ER by means of the ER retention motif, KKXX. This targeting signal conferred the predicted ER localization properties on gH in recombinant virus-infected cells, and gH and gL polypeptides failed to become processed to their mature forms. Cells infected with the recombinant virus released particles with 100-fold less infectivity than those released by cells infected with the wild-type parent virus, yet the number of enveloped virus particles released into the medium was unaltered. These particles contained normal amounts of gD and VP16 but did not contain detectable amounts of gH, and these data are consistent with a model of virus exit whereby naked nucleocapsids in the cytoplasm acquire their final envelope from a subcellular compartment other than the ER-inner nuclear membrane.     

Screening of a high growth influenza B virus strain in Vero cells

Due to the insufficient supply of embryonated chicken eggs, the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus. The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines. However, most of the influenza viruses can not grow well in Vero cells. To develop a new influenza vaccine with Vero cells as a substrate, the virus needs to adapt to this cell substrate to maintain high growth characteristics. By serial passages in Vero cells, the B/Yunnan/2/2005va (B) strain was successfully adapted to Vero cells, with the hemagglutination titer (HAT) of the virus reaching 1:512. The high growth characteristic of this strain is stable up to 21 passages. The strain was identified by hemagglutination inhibition (HAI) test and sequencing respectively; the HA₁ gene sequence of the virus was cloned and analyzed. The screening and establishment of high growth B virus provides an important tool for influenza vaccine production in Vero cells.     

Isolation of a lethal rhabdovirus from the cultured Chinese sucker Myxocyprinus asiaticus

A rhabdovirus was found to be associated with a lethal hemorrhagic disease in the cultured Chinese sucker Myxocyprinus asiaticus Bleeker. The rhabdovirus was amplified and isolated from the infected GCO (grass carp ovary) cells. In ultrathin sections of liver cells from the diseased fish, the virus particles exhibited the characteristic bacilliform morphology, and budded through vesicle membranes of the infected cells. The isolated rhabdovirus particles were found to have a bacilliform morphology with 2 rounded ends rather than a typical flat base. The virus particles were measured and ranged in size from 150 to 200 nm in length and 50 to 60 nm in diameter. Most other characteristics, including their size, extensive virus infectivity to fish cell lines, strong cytopathogenic effects, stability at high temperatures, vesicle formation in infected cells, structure protein electrophoretic patterns and the presence of an RNA genome, very closely resembled those of other fish rhabdoviruses. At present it is not known if this is a novel virus species or if it is an isolate of a known fish rhabdovirus. Until a confirmed identification can be made, we will temporarily refer to this virus as Chinese sucker rhabdovirus (CSRV).