Deep Lake, Antarctica, is a hypersaline lake characterized by a very low microbial diversity, dominated by archaea, and a lack of grazing organisms, making viruses important players in regulating community structure. Here we present an in-depth characterization of an archaeal virus-host system isolated from Deep Lake. Upon purifying the environmental virus lysate through plaque assays, with the intention to generate a clean and stable virus-host system, we select for a virus variant with an exclusively lytic life cycle (HRTV-DL1). The host Halorubrum lacusprofundi exhibits a large arsenal of virus exclusion mechanisms, indicating a long ongoing arms race with viruses. However, we uncover that the majority of this arsenal was lost spontaneously in a strain grown under non-challenging laboratory conditions. By challenging both the parental strain and the sensitive strain with HRTV-DL1, we discovered a number of putative virus exclusion mechanisms that are only activated in the sensitive strain upon the lack of defense systems present in the parental strain. We identify one of two S-layer proteins as primary receptor for HRTV-DL1 and conclude that the presence of two different S-layer proteins in one strain provides a strong advantage in the arms race with viruses. We propose the involvement of origin recognition proteins (ORC1/CDC6) in virus exclusion. While Hrr. lacusprofundi and HRTV-DL1 represent a great archaeal model system to observe the arms race between viruses and hosts, our work also demonstrates that an isolated model virus-host systems does not reflect the entire spectrum of interactions as they occur in the environment.