Co-evolution of bats and viruses and how it has shaped host biology

Although the general link between bats and viral diseases is clear, tracing outbreaks to their bat origins can be difficult. It is believed that the lack of symptoms in bats may be caused by their long co-evolution with viruses, their immunological traits, or evolutionary adjustments arising from endogenized viral genes. Our work confirmed that, despite a small genome size, bats have a comparable diversity of endogenous retroviruses (ERVs) to other mammals. Some of these ERVs are suffi- ciently preserved to be expressed, with potential effects for host biology. We detected an unusual diversity of complex retroviruses, which are generally rare in endogenous form, and a novel class of recombinant retrovirus with an alpharetrovirus-like envelope which has not previously been seen in mammalian genomes. In parallel we studied Toll-like receptors (TLRs) in bats, a class of innate immunity recep- tors. Although highly conserved in vertebrates, the viral and bacterial ligand recognition properties of TLRs can have subtle variations between species, which may have driven the evolutionary pathways of interactions with infectious diseases. We found that bat species differ between each other with respect to the array of TLR genes and discuss these in the context of a broader mammalian profile. In addition, we studied the mammalian ACE2 receptor, which is an entry receptor for SARS viruses. With coronaviruses which can change tropism quickly, the host range can at least partially be predicted with knowledge of the receptor specificity. We analysed the ACE2 SARS binding region of several vertebrates and discovered that it can vary even between related species e.g. bats. Collectively these results strengthen the unique position the Chiroptera order has in regards to its relationship with viruses, both exogenous and endogenous and confirm the special role of bats among other mammals as virus reservoirs.</p

The evolution of endogenous retroviral envelope genes in bats and their potential contribution to host biology

Bats are the primary reservoirs and carriers of a wide range of viruses of unknown infectivity and pathogenic potential. Some of those if transmitted to other species can cause enormous economic losses in agriculture, and mortality in humans. Bats can be persistently infected with viruses while not showing any symptoms of disease, despite having high virus titre levels in their tissues and shedding virions for months or years after primary infection. It has been suggested that the lack of symptoms of viral infections and low mortality rate in bats might be due to immune adaptations that result from their long-term co-evolution with viruses. In this study, we screened all publicly available bat genomes from six bat families within which we have identified several envelope sequences of retroviral origin (gammaretroviruses). We analysed the identified sequences with Bayesian methods and maximum-likelihood inference to generate a phylogenetic tree with additional reference sequences of known endogenous and exogenous viral envelope genes. We also identified groups of orthologous viral envelopes and analysed them to determine if any of them might be an EVE (endogenous virus element) with an EDI (EVE- derived immunity) function or a candidate for a bat syncytin gene, which is an endogenized viral envelope, mostly known from its function in placentation in animals. Our study shows that bat genomes contain a substantial number of large, intact envelopes with open reading frames, which were found clustering closely on a phylogenetic tree reconstruction with syncytin sequences of other species. That might indicate that such sequences are good candidates for further bat-syncytin/EDI search

The potential role of endogenous viral elements in the evolution of bats as reservoirs for zoonotic viruses

Despite a small genome size, bats have comparable diversity of retroviral and non-retroviral endogenous sequences to other mammals. These include Class I and Class II retroviral sequences, foamy viruses, and deltaretroviruses, as well as filovirus, bornavirus, and parvovirus endogenous viral elements. Some of these endogenous viruses are sufficiently preserved in bat genomes to be expressed, with potential effects for host biology. It is clear that the bat immune system differs when compared with other mammals, yet the role that virus-derived endogenous elements may have played in the evolution of bat immunity is poorly understood. In this review, we discuss some of the bat-specific immune mechanisms that may have resulted in a virus-tolerant phenotype and link these to the long-standing virus-host coevolution that may have allowed a large diversity of endogenous retroviruses and other endogenous viral elements to colonize bat genomes. We also consider the possible effects of endogenization in the evolution of the bat immune system