
The purpose of this paper is to give some sufficient conditions for the existence of periodic oscillation of a class of in-host MERS-Cov infection model with cytotoxic T lymphocyte (CTL) immune response. A new technique is developed to obtain a lower bound of the state variable characterizing CTL immune response in the model. Our results expand on some previous works.
Citation: Tuersunjiang Keyoumu, Ke Guo, Wanbiao Ma. Periodic oscillation for a class of in-host MERS-CoV infection model with CTL immune response[J]. Mathematical Biosciences and Engineering, 2022, 19(12): 12247-12259. doi: 10.3934/mbe.2022570
[1] | Cameron Browne . Immune response in virus model structured by cell infection-age. Mathematical Biosciences and Engineering, 2016, 13(5): 887-909. doi: 10.3934/mbe.2016022 |
[2] | Khalid Hattaf, Noura Yousfi . Dynamics of SARS-CoV-2 infection model with two modes of transmission and immune response. Mathematical Biosciences and Engineering, 2020, 17(5): 5326-5340. doi: 10.3934/mbe.2020288 |
[3] | Ting Guo, Zhipeng Qiu . The effects of CTL immune response on HIV infection model with potent therapy, latently infected cells and cell-to-cell viral transmission. Mathematical Biosciences and Engineering, 2019, 16(6): 6822-6841. doi: 10.3934/mbe.2019341 |
[4] | Chentong Li, Jinhu Xu, Jiawei Liu, Yicang Zhou . The within-host viral kinetics of SARS-CoV-2. Mathematical Biosciences and Engineering, 2020, 17(4): 2853-2861. doi: 10.3934/mbe.2020159 |
[5] | A. M. Elaiw, A. S. Shflot, A. D. Hobiny . Stability analysis of general delayed HTLV-I dynamics model with mitosis and CTL immunity. Mathematical Biosciences and Engineering, 2022, 19(12): 12693-12729. doi: 10.3934/mbe.2022593 |
[6] | Xuejuan Lu, Lulu Hui, Shengqiang Liu, Jia Li . A mathematical model of HTLV-I infection with two time delays. Mathematical Biosciences and Engineering, 2015, 12(3): 431-449. doi: 10.3934/mbe.2015.12.431 |
[7] | Jiawei Deng, Ping Jiang, Hongying Shu . Viral infection dynamics with mitosis, intracellular delays and immune response. Mathematical Biosciences and Engineering, 2023, 20(2): 2937-2963. doi: 10.3934/mbe.2023139 |
[8] | Suqi Ma . Low viral persistence of an immunological model. Mathematical Biosciences and Engineering, 2012, 9(4): 809-817. doi: 10.3934/mbe.2012.9.809 |
[9] | Abdessamad Tridane, Yang Kuang . Modeling the interaction of cytotoxic T lymphocytes and influenza virus infected epithelial cells. Mathematical Biosciences and Engineering, 2010, 7(1): 171-185. doi: 10.3934/mbe.2010.7.171 |
[10] | A. M. Elaiw, Raghad S. Alsulami, A. D. Hobiny . Global dynamics of IAV/SARS-CoV-2 coinfection model with eclipse phase and antibody immunity. Mathematical Biosciences and Engineering, 2023, 20(2): 3873-3917. doi: 10.3934/mbe.2023182 |
The purpose of this paper is to give some sufficient conditions for the existence of periodic oscillation of a class of in-host MERS-Cov infection model with cytotoxic T lymphocyte (CTL) immune response. A new technique is developed to obtain a lower bound of the state variable characterizing CTL immune response in the model. Our results expand on some previous works.
Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV). The intermediate host of MERS-CoV is probably the dromedary camel, a zoonotic virus [1]. Most MERS cases are acquired by human-to-human transmission. There is no vaccine or specific treatment available, and approximately 35% of patients with MERS-CoV infection have died [2]. There has been extensive works on infectious disease models and viral infection models associated with MERS that can help in disease control and provide strategies for potential drug treatments [3,4,5,6,7,8].
Dipeptidyl peptidase-4 (DPP4) plays an important role in viral infection [2]. Based on classic viral infection models developed in [9,10,11], a four-dimensional ordinary differential equation model is proposed and studied in [8]. The model in [8] describes the interaction mechanisms among uninfected cells, infected cells, DPP4 and MERS-CoV.
Recently, taking into account periodic factors such as diurnal temperature differences and periodic drug treatment, the model in [8] has been further extended a periodic case in [12], and then the existence of positive periodic solutions is studied by using the theorem in [13].
It is well-known that CTL immune responses play a very critical role in controlling viral load and the concentration of infected cells. Thus, many scholars have considered CTL immune responses in various viral infection models and have achieved many excellent research results [14,15,16,17,18]. CTL cells can kill virus-infected cells and are important for the control and clearance of MERS-CoV infections [19]. Inspired by the above research works, we consider the following periodic MERS-CoV infection model with CTL immune response:
{˙T(t)=λ(t)−β(t)D(t)v(t)T(t)−d(t)T(t),˙I(t)=β(t)D(t)v(t)T(t)−d1(t)I(t)−p(t)I(t)Z(t),˙v(t)=d1(t)M(t)I(t)−c(t)v(t),˙D(t)=λ1(t)−β1(t)β(t)D(t)v(t)T(t)−γ(t)D(t),˙Z(t)=q(t)I(t)Z(t)−b(t)Z(t). | (1.1) |
In model (1.1), T(t), I(t), v(t), D(t) and Z(t) represent the concentrations of uninfected cells, infected cells, free virus, DPP4 on the surface of uninfected cells and CTL cells at time t, respectively. CTL cells increase at a rate bilinear rate q(t)I(t)Z(t) by the viral antigen of the infected cells and decay at rate b(t)Z(t); infected cells are killed by the CTL immune response at rate p(t)I(t)Z(t). Except for p(t), q(t) and b(t), all the remaining parameters of model (1.1) have the same biological meanings as in [12].
Throughout the paper, it is assumed that the functions λ(t), β(t), d(t), d1(t), p(t), M(t), c(t), λ1(t), γ(t), q(t) and b(t) are positive, continuous and ω periodic (ω>0); the function β1(t) is non-negative, continuous and ω periodic.
From point of view in both biology and mathematics, it is one of the most significant topics to study the existence of periodic oscillations of a system (see, for example, [12,20,21,22,23,24,25,26] and the references therein).
In the next section, some sufficient criteria are given for the existence of positive periodic oscillations of model (1.1). It should be mentioned here that, in the proofs of the main results in the following section, a new technique is developed to obtain a lower bound of the state variable Z(t) characterizing CTL immune response in model (1.1).
For some function f(t) which is continuous and ω-periodic on R, let us define the following notations:
fU=maxt∈[0,ω]f(t),fl=mint∈[0,ω]f(t),ˆf=1ω∫ω0f(t)dt. |
Moreover, for convenience, let us give the following parameters:
R∗=ˆλβlexp{L3+L4}^d1exp{M2}(βlexp{L3+L4}+dU)>1,ω∗=ˆb2ˆλˆq,δ∗=^d12ˆp(R∗−1),M1=ln(λUdl),M2=ln(ˆbˆq+2ˆλω),M3=ln(^(d1M)ˆc)+M2+2ˆcω,M4=ln(λU1γl),M5=ln(ˆβexp{M1+M3+M4}ˆpexp{L2})+2ˆbω,L1=ln(λlβUexp{M3+M4}+dU),L2=ln(ˆbˆq−2ˆλω),L3=ln((^d1M)ˆc)+L2−2ˆcω,L4=ln(λl1(β1β)Uexp{M1+M3}+γU),L5=ln(δ∗)−2ˆbω. |
The following theorem is the main result of this paper.
Theorem 2.1. If R∗>1 and ω<ω∗, then model (1.1) has at least one positive ω-periodic solution.
Proof. Making the change of variables T(t)=exp{u1(t)}, I(t)=exp{u2(t)}, v(t)=exp{u3(t)}, D(t)=exp{u4(t)}, Z(t)=exp{u5(t)}, then model (1.1) can be rewritten as
{˙u1(t)=λ(t)exp{u1(t)}−β(t)exp{u3(t)+u4(t)}−d(t),˙u2(t)=β(t)exp{u1(t)+u3(t)+u4(t)}exp{u2(t)}−d1(t)−p(t)exp{u5(t)},˙u3(t)=d1(t)M(t)exp{u2(t)}exp{u3(t)}−c(t),˙u4(t)=λ1(t)exp{u4(t)}−β1(t)β(t)exp{u1(t)+u3(t)}−γ(t),˙u5(t)=q(t)exp{u2(t)}−b(t). | (2.1) |
Thus, we only need to consider model (2.1).
Let us set
X=Y={u=(u1(t),u2(t),u3(t),u4(t),u5(t))T∈C(R,R5)|u(t)=u(t+ω)} |
with the norm
||u||=maxt∈[0,ω]|u1(t)|+maxt∈[0,ω]|u2(t)|+maxt∈[0,ω]|u3(t)|+maxt∈[0,ω]|u4(t)|+maxt∈[0,ω]|u5(t)|. |
It can be shown that X and Y are Banach spaces. Define
Nu=[λ(t)exp{u1(t)}−β(t)exp{u3(t)+u4(t)}−d(t)β(t)exp{u1(t)+u3(t)+u4(t)}exp{u2(t)}−d1(t)−p(t)exp{u5(t)}d1(t)M(t)exp{u2(t)}exp{u3(t)}−c(t)λ1(t)exp{u4(t)}−β1(t)β(t)exp{u1(t)+u3(t)}−γ(t)q(t)exp{u2(t)}−b(t)]:=[N1(t)N2(t)N3(t)N4(t)N5(t)](u∈X), |
Lu=˙u(u∈DomL),Pu=1ω∫ω0u(t)dt(u∈X),Qu=1ω∫ω0u(t)dt(u∈Y), |
here DomL={u∈X,˙u∈X}. It easily has that KerL={u∈X|u∈R5} and ImL={u∈Y|∫ω0u(t)dt=0}. Further, it is clear that ImL is closed in Y and dimKerL=codimImL=5. Hence, L is a Fredholm mapping with index zero.
For μ∈(0,1), let us consider the equation Lu=μNu, i.e.,
{˙u1(t)=μ[λ(t)exp{u1(t)}−β(t)exp{u3(t)+u4(t)}−d(t)],˙u2(t)=μ[β(t)exp{u1(t)+u3(t)+u4(t)}exp{u2(t)}−d1(t)−p(t)exp{u5(t)}],˙u3(t)=μ[d1(t)M(t)exp{u2(t)}exp{u3(t)}−c(t)],˙u4(t)=μ[λ1(t)exp{u4(t)}−β1(t)β(t)exp{u1(t)+u3(t)}−γ(t)],˙u5(t)=μ[q(t)exp{u2(t)}−b(t)]. | (2.2) |
For any solution u=(u1(t),u2(t),u3(t),u4(t),u5(t))T∈X of (2.2), it has
{∫ω0[λ(t)exp{u1(t)}−β(t)exp{u3(t)+u4(t)}−d(t)]dt=0,∫ω0[β(t)exp{u1(t)+u3(t)+u4(t)}exp{u2(t)}−d1(t)−p(t)exp{u5(t)}]dt=0,∫ω0[d1(t)M(t)exp{u2(t)}exp{u3(t)}−c(t)]dt=0,∫ω0[λ1(t)exp{u4(t)}−β1(t)β(t)exp{u1(t)+u3(t)}−γ(t)]dt=0,∫ω0[q(t)exp{u2(t)}−b(t)]dt=0. | (2.3) |
From the first two equations in (2.2), it has
˙u1(t)exp{u1(t)}=μ[λ(t)−β(t)exp{u1(t)+u3(t)+u4(t)}−d(t)exp{u1(t)}], |
and
˙u2(t)exp{u2(t)}=μ[β(t)exp{u1(t)+u3(t)+u4(t)}−d1(t)exp{u2(t)}−p(t)exp{u2(t)+u5(t)}]. |
Hence, by integrating the above two equations on [0,ω], it has
∫ω0[λ(t)−β(t)exp{u1(t)+u3(t)+u4(t)}−d(t)exp{u1(t)}]dt=0 | (2.4) |
and
∫ω0[β(t)exp{u1(t)+u3(t)+u4(t)}−d1(t)exp{u2(t)}−p(t)exp{u2(t)+u5(t)}]dt=0. | (2.5) |
Note that I(t):=exp{u2(t)} satisfies
˙I(t)=˙u2(t)exp{u2(t)}=μ[β(t)exp{u1(t)+u3(t)+u4(t)}−d1(t)−p(t)exp{u2(t)+u5(t)}]. |
Then, from (2.4) and (2.5), it has
∫ω0|˙I(t)|dt≤μ∫ω0[β(t)exp{u1(t)+u3(t)+u4(t)}+d1(t)+p(t)exp{u2(t)+u5(t)}]dt≤2∫ω0β(t)exp{u1(t)+u3(t)+u4(t)}dt≤2ˆλω. | (2.6) |
From the third and the fifth equations of (2.2), it has
∫ω0|˙u3(t)|dt≤μ[∫ω0d1(t)M(t)exp{u2(t)}exp{u3(t)}dt+∫ω0c(t)dt]<2ˆcω,∫ω0|˙u5(t)|dt≤μ[∫ω0q(t)exp{u2(t)}dt+∫ω0b(t)dt]<2ˆbω. | (2.7) |
Note that u∈X, there exist ξi,ηi∈[0,ω] (i=1,2,3,4,5), such that
ui(ξi)=mint∈[0,ω]ui(t),ui(ηi)=maxt∈[0,ω]ui(t)(i=1,2,3,4,5). |
From (2.2), ˙u1(η1)=0 and ˙u4(η4)=0, it has
λ(η1)exp{u1(η1)}−β(η1)exp{u3(η1)+u4(η1)}−d(η1)=0,λ1(η4)exp{u4(η4)}−β1(η4)β(η4)exp{u1(η4)+u3(η4)}−γ(η4)=0, |
which imply that
u1(t)≤u1(η1)≤ln(λ(η1)d(η1))≤ln(λUdl)=M1,u4(t)≤u4(η4)≤ln(λ1(η4)γ(η4))≤ln(λU1γl)=M4. | (2.8) |
From the last equation of (2.3), it has
∫ω0q(t)exp{u2(ξ2)}dt≤ˆbω≤∫ω0q(t)exp{u2(η2)}dt, |
which implies that
I(ξ2)=exp{u2(ξ2)}≤ˆbˆq≤exp{u2(η2)}=I(η2). |
Then, from (2.6) and ω<ω∗, it has
I(t)≤I(ξ2)+∫ω0|˙I(t)|dt≤ˆbˆq+2ˆλω,I(t)≥I(η2)−∫ω0|˙I(t)|dt≥ˆbˆq−2ˆλω=2ˆλ(ω∗−ω)>0. |
Thus, it has
u2(t)≤ln(ˆbˆq+2ˆλω)=M2,u2(t)≥ln(ˆbˆq−2ˆλω)=L2. | (2.9) |
From the third equation of (2.3), it has
∫ω0d1(t)M(t)exp{M2}exp{u3(ξ3)}dt≥ˆcω≥∫ω0d1(t)M(t)exp{L2}exp{u3(η3)}dt, |
which implies that
u3(ξ3)≤ln(^(d1M)ˆc)+M2,u3(η3)≥ln(^(d1M)ˆc)+L2. |
Then, from (2.7), it has
u3(t)≤u3(ξ3)+∫ω0|˙u3(t)|dt≤ln(^(d1M)ˆc)+M2+2ˆcω=M3,u3(t)≥u3(η3)−∫ω0|˙u3(t)|dt≥ln(^(d1M)ˆc)+L2−2ˆcω=L3. | (2.10) |
From the second equation of (2.3), it has
ˆpexp{u5(ξ5)}ω≤∫ω0[β(t)exp{M1+M3+M4}exp{L2}−d1(t)]dt≤exp{M1+M3+M4}exp{L2}ˆβω, |
which implies that
u5(ξ5)≤ln(ˆβexp{M1+M3+M4}ˆpexp{L2}):=l5. |
Then, from (2.7), it has
u5(t)≤u5(ξ5)+∫ω0|˙u5(t)|dt≤l5+2ˆbω=M5. |
From ˙u1(ξ1)=0, ˙u4(ξ4)=0, (2.8) and (2.10), it has
exp{u1(ξ1)}=λ(ξ1)β(ξ1)exp{u3(ξ1)+u4(ξ1)}+d(ξ1)≥λlβUexp{M3+M4}+dU,exp{u4(ξ4)}=λ1(ξ4)β1(ξ4)β(ξ4)exp{u1(ξ4)+u3(ξ4)}+γ(ξ4)≥λl1(β1β)Uexp{M1+M3}+γU. |
Thus, it has
u1(t)≥u1(ξ1)≥ln(λlβUexp{M3+M4}+dU)=L1,u4(t)≥u4(ξ4)=ln(λl1(β1β)Uexp{M1+M3}+γU)=L4. | (2.11) |
Let us give an estimate of the lower bound of the state variable u5(t) related to CTL immune response. It should be mentioned here that a completely different method from that in [12] has been used.
Claim A If R∗>1 and ω<ω∗, then
exp{u5(η5)}≥δ∗. |
If Claim A is not true, then it has that, for any t, exp{u5(t)}≤exp{u5(η5)}<δ∗. Hence, it has from (2.3), (2.9)–(2.11) that
0=∫ω0[β(t)exp{u1(t)+u3(t)+u4(t)}exp{u2(t)}−d1(t)−p(t)exp{u5(t)}]dt≥∫ω0[β(t)exp{u1(t)+L3+L4}exp{M2}−d1(t)−p(t)exp{u5(η5)}]dt≥βlexp{L3+L4}exp{M2}∫ω0exp{u1(t)}dt−(ˆd1+ˆpδ∗)ω, |
which implies that
∫ω0d(t)exp{u1(t)}dt≤dU∫ω0exp{u1(t)}dt≤dU(ˆd1+ˆpδ∗)exp{M2}βlexp{L3+L4}ω:=Ψω. | (2.12) |
Adding (2.4) and (2.5) together, it has
∫ω0[λ(t)−d(t)exp{u1(t)}]dt=∫ω0[d1(t)exp{u2(t)}+p(t)exp{u2(t)+u5(t)}]dt≤∫ω0exp{M2}[d1(t)+p(t)exp{u5(η5)}]dt≤exp{M2}(^d1+ˆpδ∗)ω, |
which implies that
∫ω0d(t)exp{u1(t)}dt≥[ˆλ−exp{M2}(^d1+ˆpδ∗)]ω=Ψω+[ˆλ−Ψ−exp{M2}(^d1+ˆpδ∗)]ω=Ψω+[ˆλ−exp{M2}(1+dUβlexp{L3+L4})(^d1+ˆpδ∗)]ω=Ψω+^d1exp{M2}(1+dUβlexp{L3+L4})(R∗−1−ˆp^d1δ∗)ω=Ψω+^d12exp{M2}(1+dUβlexp{L3+L4})(R∗−1)ω>Ψω, |
which is a contradiction to (2.12). Thus, the claim holds.
From Claim A and (2.7), it has
u5(t)≥u5(η5)−∫ω0|˙u5(t)|dt≥ln(δ∗)−2ˆbω=L5. | (2.13) |
Now, for convenience, let us define
¯R∗=(ˆλ−^d1ˆbˆq)ˆβ^(d1M)ˆd^d1ˆc^λ1^(β1β)ˆλ^(d1M)ˆbˆdˆcˆq+ˆγ,Zmax=ˆqˆpˆb(ˆλ−^d1ˆbˆq). |
Note that if R∗>1, then it has
~R∗:=(ˆλ−^d1exp{M2})βlexp{L3+L4}dU^d1exp{M2}>1, |
which implies that
Zmax>ˆqˆpˆb[ˆλ−^d1(ˆbˆq+2ˆλω)]=ˆqˆpˆb(ˆλ−^d1exp{M2})>0,¯R∗≥(ˆλ−^d1ˆbˆq)ˆβ^(d1M)ˆd^d1ˆcλl1(β1β)Uexp{M3+M1}+γU≥~R∗>1. |
Let (u1,u2,u3,u4,u5)T∈R5 be the solution of the following equations:
{ˆλexp{u1}−ˆβexp{u3+u4}−ˆd=0,ˆβexp{u1+u3+u4}exp{u2}−ˆd1−ˆpexp{u5}=0,^(d1M)exp{u2}exp{u3}−ˆc=0,ˆλ1exp{u4}−^(β1β)exp{u1+u3}−ˆγ=0,ˆqexp{u2}−ˆb=0.. | (2.14) |
Define Γ:[0,Zmax]→R, via
Γ(x)=ˆβ^(d1M)ˆc^λ1Γ1(x)^(β1β)Γ1(x)^(d1M)ˆbˆqˆc+ˆγ−ˆd1−ˆpx, |
where
Γ1(x)=ˆλˆd−^d1ˆbˆdˆq−ˆpˆbˆdˆqx=ˆpˆbˆdˆq(Zmax−x). |
Equation (2.14) can be rewritten as
exp{u2}=ˆbˆq,exp{u3}=^(d1M)ˆcexp{u2}=^(d1M)ˆbˆqˆc,exp{u1}=ˆλˆd−^d1exp{u2}ˆd−ˆpexp{u2}ˆdexp{u5}=Γ1(exp{u5}),exp{u4}=^λ1^(β1β)exp{u1+u3}+ˆγ=^λ1^(β1β)Γ1(exp{u5})^(d1M)ˆbˆqˆc+ˆγ,ˆβ^(d1M)ˆcexp{u1+u4}−ˆd1−ˆpexp{u5}=Γ(exp{u5})=0. |
It is obvious that if there is a solution (u1,u2,u3,u4,u5)T∈R5 for (2.14), it must have 0<exp{u5}<Zmax. In addition, note that Γ(x) is monotonically decreasing with respect to x on [0,Zmax]. It has from Γ(Zmax)=−^d1−ˆpZmax<0 and
Γ(0)=ˆβ^(d1M)ˆc^λ1Γ1(0)^(β1β)Γ1(0)^(d1M)ˆbˆqˆc+ˆγ−^d1>ˆβ^(d1M)ˆc^λ1(ˆλˆd−^d1ˆbˆdˆq)^(β1β)ˆλˆd^(d1M)ˆbˆqˆc+ˆγ−^d1=^d1(¯R∗−1)>0 |
that there exists a unique positive constant x=Z∗∈(0,Zmax) such that Γ(Z∗)=0.
The above discussions show that, if R∗>1, (2.14) has a unique solution (u∗1,u∗2,u∗3,u∗4,u∗5)T, here u∗i=ln(ei) (i=1,2,3,4,5),
e1=Γ1(Z∗)>0,e2=ˆbˆq>0,e3=^(d1M)ˆbˆqˆc>0,e4=^λ1^(β1β)Γ1(Z∗)^(d1M)ˆbˆqˆc+ˆγ>0,e5=Z∗>0. |
Let us define the following set
Ω={u∈X|||u||<U1=1+5∑i=1(max{|Mi|,|Li|}+|u∗i|)}⊂X. |
Moreover, by similar arguments as in [12], it has that N is L-compact on ¯Ω.
Now, let us compute the Leray-Schauder degree deg{QN,∂Ω∩KerL,(0,0,0,0,0)T}:=Δ as follows,
Δ=sign|−ˆλe10−ˆβe3e4−ˆβe3e40ˆβe1e3e4e2−ˆβe1e3e4e2ˆβe1e3e4e2ˆβe1e3e4e2−ˆpe50^(d1M)e2e3−^(d1M)e2e300−^(β1β)e1e30−^(β1β)e1e3−^λ1e400ˆqe2000|=sign{−^(d1M)ˆpˆqe22e5e3(ˆλ^λ1e1e4−ˆβ^(β1β)e1e23e4)}=sign{−^(d1M)ˆpˆqe22e5e3e1e4[ˆde1(^(β1β)e1e3e4+ˆγe4)+ˆβˆγe1e3e24]}=−1≠0, |
where ˆλ=ˆβe1e3e4+ˆde1 and ^λ1=^(β1β)e1e3e4+ˆγe4 are used.
Finally, it has those all the conditions of the continuation theorem in [13] (also see, for example, Lemma 2.1 in [12]) are satisfied. This proves that, if ω<ω∗ and R∗>1, model (2.1) has at least one ω-periodic solution.
Let us consider the following classical viral infection dynamic model [9] with CTL immune response:
{˙T(t)=λ(t)−β(t)v(t)T(t)−d(t)T(t),˙I(t)=β(t)v(t)T(t)−d1(t)I(t)−p(t)I(t)Z(t),˙v(t)=d1(t)M(t)I(t)−c(t)v(t),˙Z(t)=q(t)I(t)Z(t)−b(t)Z(t),(A) |
where, all the coefficients are the same with that in model (1.1).
Define R1:[0,ω∗]→R, via
R1(x)=ˆλβl[^(d1M)ˆcexp{−2ˆcx}(ˆbˆq−2ˆλx)]^d1(ˆbˆq+2ˆλx){dU+βl[^(d1M)ˆcexp{−2ˆcx}(ˆbˆq−2ˆλx)]}. |
Obviously, R1(x) is monotonically decreasing on [0,ω∗] and
R1(0)=ˆλβl^(d1M)ˆq^d1(dUˆcˆq+βl^(d1M)ˆb),R1(ω∗)=0. |
Therefore, if R1(0)>1, then there exists a unique constant ω∗∗∈(0,ω∗) such that R1(ω∗∗)=1, R1(x)>1 for 0≤x<ω∗∗ and R1(x)<1 for ω∗∗<x≤ω∗.
For model (A), it is not difficult to derive the following result.
Theorem 2.2. If R1(ω)>1 and ω<ω∗ (i.e. R1(0)>1 and ω<ω∗∗<ω∗), then model (A) has at least one positive ω-periodic solution.
Remark 2.1. If all the coefficients in model (A) take constants values, i.e., λ(t)≡λ>0, β(t)≡β>0, d(t)≡d>0, d1(t)≡d1>0, p(t)≡p>0, M(t)≡M>0, c(t)≡c>0, q(t)≡q>0 and b(t)≡b>0, then model (A) becomes the classical model which is first proposed by Nowak and Bangham in [9]. the condition ω<ω∗∗ in Theorem 2.2 is naturally satisfied. Furthermore, it has R1(0)=(λβMq)/(dcq+βd1Mb):=R1. From \emph{[9]}, it has that the condition R1>1 implies the existence of a unique positive equilibrium. This shows that the conditions and conclusion in Theorem 2.2 are reasonable.
In summary, Theorem 2.1 in the paper successfully extends the main result in [12]) to a MERS-CoV viral infection model with CTL immune response. In the proof of Theorem 2.1, we use a very different method from that in [9] to obtain the lower bound (ln(δ∗)−2ˆbω) of the state variable u5(t). Furthermore, as a special case, Theorem 2.2 gives sufficient conditions for the existence of positive periodic solution of model (A). Model (A) is a natural extension of the classical model in [9]. As the end of the paper, let us give a example to summarize the applications of Theorem 2.1. Let us choose the coefficients in model (1.1) as follows (for the values of some parameters, please refer to [7,27] for the case of some autonomous models), λ(t)=45(1+0.1sin(4πt)), β(t)=1.4×10−8(1+0.1cos(4πt)), d(t)=0.001(1+0.5cos(4πt)), d1(t)=0.056(1+0.5cos(4πt)), p(t)=0.00092(1+0.5cos(4πt)), M(t)=100000, c(t)=2.1(1+0.3cos(4πt)), λ1(t)=10(1+0.1sin(4πt)), β1(t)=0.001, γ(t)=0.01(1+0.1cos(4πt)), q(t)=0.005(1+0.5sin(4πt)), b(t)=0.5(1+0.4cos(4πt)). Then, with the help of Maple mathematical software, it has ω=0.5<ω∗≈1.111111, M1≈11.502875, M2≈4.976734, M3≈14.965318, M4≈7.108426, M5≈18.976215, L1≈−0.383569, L2=4.007333, L3≈9.795917, L4≈0.623402, L5≈1.387881, R∗≈1.2170332>1. From Theorem 2.1, it follows that model (1.1) has at least one positive ω (ω=0.5)-periodic solution. Figure 1 gives the corresponding numerical simulation, and the initial value is chosen as (T(0),I(0),v(0),D(0),Z(0))T=(12.5,100,265000,995.4,423)T.
This paper is supported by National Natural Science Foundation of China (No.11971055) and Beijing Natural Science Foundation (No.1202019).
The authors declare there is no conflict of interest.
[1] |
A. M. Zaki, S. van Boheemen, T. M. Bestebroer, A. D. M. E. Osterhauset, R. A. M. Fouchier, Isolation of a novel coronavirus from a man with pneumonia in saudi arabia, N. Engl. J. Med., 367 (2012), 1814–1820. https://doi.org/10.1056/NEJMoa1211721 doi: 10.1056/NEJMoa1211721
![]() |
[2] |
A. M. Alnuqaydan, A. G. Almutary, A. Sukamaran, B. T. W. Yang, X. T. Lee, W. X. Lim, et al., Middle East Respiratory Syndrome (MERS) virus-pathophysiological axis and the current treatment strategies, AAPS PharmSciTech, 22 (2021), 173. https://doi.org/10.1208/s12249-021-02062-2 doi: 10.1208/s12249-021-02062-2
![]() |
[3] |
J. Lee, G. Chowell, E. Jung, A dynamic compartmental model for the Middle East respiratory syndrome outbreak in the Republic of Korea: A retrospective analysis on control interventions and superspreading events, J. Theor. Biol., 408 (2016), 118–126. https://doi.org/10.1016/j.jtbi.2016.08.009 doi: 10.1016/j.jtbi.2016.08.009
![]() |
[4] |
Q. Lin, A. P. Chiu, S. Zhao, D. He, Modeling the spread of Middle East respiratory syndrome coronavirus in Saudi Arabia, Stat. Methods Med. Res., 27 (2018), 1968–1978. https://doi.org/10.1177/0962280217746442 doi: 10.1177/0962280217746442
![]() |
[5] |
T. Sardar, I. Ghosh, X. Rodó, J. Chattopadhyay, A realistic two-strain model for MERS-CoV infection uncovers the high risk for epidemic propagation, PLoS Negl. Trop. Dis., 14 (2020), e0008065. https://doi.org/10.1371/journal.pntd.0008065 doi: 10.1371/journal.pntd.0008065
![]() |
[6] |
I. Ghosh, S. S. Nadim, J. Chattopadhyay, Zoonotic MERS-CoV transmission: Modeling, backward bifurcation and optimal control analysis, Nonlinear Dyn., 103 (2021), 2973–2992. https://doi.org/10.1007/s11071-021-06266-w doi: 10.1007/s11071-021-06266-w
![]() |
[7] |
K. S. Kim, K. Ejima, S. Iwanami, Y. Fujita, H. Ohashi, Y. Koizumi, et al., A quantitative model used to compare within host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2, PLoS Biol., 19 (2021), e3001128. https://doi.org/10.1371/journal.pbio.3001128 doi: 10.1371/journal.pbio.3001128
![]() |
[8] |
S. Tang, W. Ma, P. Bai, A novel dynamic model describing the spread of the MERS-CoV and the expression of dipeptidyl peptidase 4, Comput. Math. Methods Med., 2017 (2017), 5285810. https://doi.org/10.1155/2017/5285810 doi: 10.1155/2017/5285810
![]() |
[9] |
M. A. Nowak, C. R. M. Bangham, Population dynamics of immune responses to persistent viruses, Science, 272 (1996), 74–79. https://doi.org/10.1126/science.272.5258.74 doi: 10.1126/science.272.5258.74
![]() |
[10] |
A. U. Neumann, N. P. Lam, H. Dahari, D. R. Gretch, T. E. Wiley, T. J. Layden, et al., Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy, Science, 282 (1998), 103–107. https://doi.org/10.1126/science.282.5386.103 doi: 10.1126/science.282.5386.103
![]() |
[11] |
A. S. Perelson, P. W. Nelson, Mathematical analysis of HIV-1 dynamics in vivo, SIAM Rev., 41 (1999), 3–44. https://doi.org/10.1137/S0036144598335107 doi: 10.1137/S0036144598335107
![]() |
[12] |
T. Keyoumu, W. Ma, K. Guo, Existence of positive periodic solutions for a class of in-host MERS-CoV infection model with periodic coefficients, AIMS Math., 7 (2021), 3083–3096. https://doi.org/10.3934/math.2022171 doi: 10.3934/math.2022171
![]() |
[13] | R. E. Gaines, J. L. Mawhin, Coincidence Degree and Nonlinear Differential Equations, Springer-Verlag, Berlin, 1977. https://doi.org/10.1007/BFb0089537 |
[14] |
C. Egami, Bifurcation analysis of the Nowak-Bangham model in CTL dynamics, Math. Biosci., 221 (2009), 33–42. https://doi.org/10.1016/j.mbs.2009.06.005 doi: 10.1016/j.mbs.2009.06.005
![]() |
[15] |
J. Pang, J. Cui, J. Hui, The importance of immune responses in a model of hepatitis B virus, Nonlinear Dyn., 67 (2012), 723–734. https://doi.org/10.1007/s11071-011-0022-6 doi: 10.1007/s11071-011-0022-6
![]() |
[16] |
F. Li, W. Ma, Z. Jiang, D. Li, Stability and Hopf bifurcation in a delayed HIV infection model with general incidence rate and immune impairment, Comput. Math. Method Med., 2015 (2015), 206205. https://doi.org/10.1155/2015/206205 doi: 10.1155/2015/206205
![]() |
[17] |
J. Li, K. Men, Y. Yang, D. Li, Dynamical analysis on a chronic hepatitis C virus infection model with immune response, J. Theoret. Biol., 365 (2015), 337–346. https://doi.org/10.1016/j.jtbi.2014.10.039 doi: 10.1016/j.jtbi.2014.10.039
![]() |
[18] |
A. M. Elaiw, N. H. AlShamrani, Stability of HIV/HTLV-I co-infection model with delays, Math Meth Appl Sci., 45 (2022), 238–300. https://doi.org/10.1002/mma.7775 doi: 10.1002/mma.7775
![]() |
[19] |
G. Li, Y. Fan, Y. Lai, T. Han, Z. Li, P. Zhou, et al., Coronavirus infections and immune responses, J. Med. Virol., 92 (2020), 424–432. https://doi.org/10.1002/jmv.25685 doi: 10.1002/jmv.25685
![]() |
[20] |
F. Chen, D. Sun, J. Shi, Periodicity in a food-limited population model with toxicants and state dependent delays, J. Math. Anal. Appl., 288 (2003), 136–146. https://doi.org/10.1016/S0022-247X(03)00586-9 doi: 10.1016/S0022-247X(03)00586-9
![]() |
[21] |
M. Fan, Y. Kuang, Dynamics of a nonautonomous predator-prey system with the Beddington-DeAngelis functional response, J. Math. Anal. Appl., 295 (2004), 15–39. https://doi.org/10.1016/j.jmaa.2004.02.038 doi: 10.1016/j.jmaa.2004.02.038
![]() |
[22] |
K. Zhao, Y. Li, Four positive periodic solutions to two species parasitical system with harvesting terms, Comput. Math. Appl., 59 (2010), 2703–2710. https://doi.org/10.1016/j.camwa.2010.01.038 doi: 10.1016/j.camwa.2010.01.038
![]() |
[23] |
A. Muhammadhaji, Z. Teng, Global attractivity of a periodic delayed N-species model of facultative mutualism, Discrete Dyn. Nat. Soc., 2013 (2013), 580185. https://doi.org/10.1155/2013/580185 doi: 10.1155/2013/580185
![]() |
[24] |
C. Celik, N. T. Ozarslan, Existence of periodic solution for a tumor growth model with vaccine interaction, Topol. Methods Nonlinear Anal., 55 (2020), 37–49. https://doi.org/10.12775/TMNA.2019.083 doi: 10.12775/TMNA.2019.083
![]() |
[25] |
K. Guo, K. Song, W. Ma, Existence of positive periodic solutions of a delayed periodic Microcystins degradation model with nonlinear functional responses, Appl. Math. Lett., 131 (2022), 108056. https://doi.org/10.1016/j.aml.2022.108056 doi: 10.1016/j.aml.2022.108056
![]() |
[26] |
J. Yang, R. Xu, H. Sun, Dynamics of a seasonal brucellosis disease model with nonlocal transmission and spatial diffusion, Commun. Nonlinear Sci. Numer. Simul., 94 (2021), 105551. https://doi.org/10.1016/j.cnsns.2020.105551 doi: 10.1016/j.cnsns.2020.105551
![]() |
[27] |
C. Li, J. Xu, J. Liu, Y. Zhou, The within-host viral kinetics of SARS-CoV-2, Math. Biosci. Eng., 17 (2020), 2853–2861. https://doi.org/10.3934/mbe.2020159 doi: 10.3934/mbe.2020159
![]() |
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