Bat humoral immunity and its role in viral pathogenesis, transmission, and zoonosis

Abstract

Bats harbor viruses that can cause severe disease and death in humans including filoviruses (e.g., Ebola virus), henipaviruses (e.g., Hendra virus), and coronaviruses (e.g., SARS-CoV). Bats often tolerate these viruses without noticeable adverse immunological effects or succumbing to disease. Previous studies have largely focused on the role of the bat's innate immune response to control viral pathogenesis, but little is known about bat adaptive immunity. A key component of adaptive immunity is the humoral response, comprised of antibodies that can specifically recognize viral antigens with high affinity. The antibody genes within the 1,400 known bat species are highly diverse, and these genetic differences help shape fundamental aspects of the antibody repertoire, including starting diversity and viral antigen recognition. Whether antibodies in bats protect, mediate viral clearance, and prevent transmission within bat populations is poorly defined. Furthermore, it is unclear how neutralizing activity and Fc-mediated effector functions contribute to bat immunity. Although bats have canonical Fc genes (e.g., mu, gamma, alpha, and epsilon), the copy number and sequences of their Fc genes differ from those of humans and mice. The function of bat antibodies targeting viral antigens has been speculated based on sequencing data and polyclonal sera, but functional and biochemical data of monoclonal antibodies are lacking. In this review, we summarize current knowledge of bat humoral immunity, including variation between species, their potential protective role(s) against viral transmission and replication, and address how these antibodies may contribute to population dynamics within bats communities. A deeper understanding of bat adaptive immunity will provide insight into immune control of transmission and replication for emerging viruses with the potential for zoonotic spillover.

Keywords: Chiroptera; bat immunity; humoral responses; immunoglobulin repertoire; infectious diseases.

Figure 1

Bat species distribution and viral families. (A) Bats are diverse, with families that inhabit disparate regions across the globe. Calogram at the family level [adapated from (11)] at the family level. Colors correspond to families with named species in the text; named species are specified in colored boxes. Species distribution data from IUCN (2023) (12). (B) Bat viruses are similarly diverse. Species viral data from DBatVir (2023) (13). Proportions were calculated as the number of viruses (as per NCBI taxonomy) in each viral family per total number of viruses recorded for named species in the family.

Figure 2

Immunoglobulin loci organization and gene abundance. (A) The variable region of antibodies is comprised of somatically rearranged V, D, and J (heavy chain) or V and J (light chain) genes. During somatic rearrangement, diversity is further introduced in the junctions between rearranged genes through the addition of non-templated P and N nucleotides (light green). The complementarity-determining regions (CDRs) are shown for both heavy and light chains. The heavy chain CDRs for antibody CH67 (PDB 4HKB) are highlighted in blue. (B) Functional V gene abundances are variable between species (*gene conversion). (C) Ig gene organization is unique for Egyptian rousette bats (ERBs) where D and J genes are interspersed rather than sequential (21), as seen in human and mouse Ig loci (22).