  A current challenge for disease modeling and public health is understanding
pathogen dynamics across scales since their ecology and evolution ultimately
operate on several coupled scales. This is particularly true for vector-borne
diseases, where within-vector, within-host, and between vector-host populations
all play crucial roles in diversity and distribution of the pathogen. Despite
recent modeling efforts to determine the effect of within-host virus-immune
response dynamics on between-host transmission, the role of within-vector viral
dynamics on disease spread is overlooked. Here we formulate an
age-since-infection structured epidemic model coupled to nonlinear ordinary
differential equations describing within-host immune-virus dynamics and
within-vector viral kinetics, with feedbacks across these scales. We first
define the \emph{within-host viral-immune response and within-vector viral
kinetics dependent} basic reproduction number $\mathcal R_0.$ Then we prove
that whenever $\mathcal R_0<1,$ the disease free equilibrium is locally
asymptotically stable, and under certain biologically interpretable conditions,
globally asymptotically stable. Otherwise if $\mathcal R_0>1,$ it is unstable
and the system has a unique positive endemic equilibrium. In the special case
of constant vector to host inoculum size, we show the positive equilibrium is
locally asymptotically stable and the disease is weakly uniformly persistent.
Furthermore numerical results suggest that within-vector-viral kinetics and
dynamic inoculum size may play a substantial role in epidemics. Finally, we
address how the model can be utilized to better predict the success of control
strategies such as vaccination and drug treatment.
