Rabies has affected mankind for several centuries and is one of the oldest known zoonoses.
It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the
immune response and kills its host. This review investigates the complex interplay between RABV
and the immune system, including the various means by which RABV evades, or advantageously
utilizes, the host immune response in order to ensure successful replication and spread to another host.
Different factors that influence immune responses—including age, sex, cerebral lateralization and
temperature—are discussed, with specific reference to RABV and the effects on host morbidity and
mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial
mechanism of the host’s response to infection. The various RABV proteins and their roles in immune
evasion are examined in depth with reference to important domains and the downstream effects
of these interactions. Lastly, an overview of the means by which RABV evades important immune
responses is provided. The research discussed in this review will be important in determining the
roles of the immune response during RABV infections as well as to highlight important therapeutic
target regions and potential strategies for rabies treatment.