B Cell Response to Herpesvirus Infection of the Olfactory Neuroepithelium

Abstract

Viruses commonly infect the respiratory tract. Analyses of host defense have focused on the lungs and the respiratory epithelium. Spontaneously inhaled murid herpesvirus 4 (MuHV-4) and herpes simplex virus 1 (HSV-1) instead infect the olfactory epithelium, where neuronal cilia are exposed to environmental antigens and provide a route across the epithelial mucus. We used MuHV-4 to define how B cells respond to virus replication in this less well-characterized site. Olfactory infection elicited generally weaker acute responses than lung infection, particularly in the spleen, reflecting slower viral replication and spread. Few virus-specific antibody-forming cells (AFCs) were found in the nasal-associated lymphoid tissue (NALT), a prominent response site for respiratory epithelial infection. Instead, they appeared first in the superficial cervical lymph nodes. The focus of the AFC response then moved to the spleen, matching the geography of virus dissemination. Little virus-specific IgA response was detected until later in the bone marrow. Neuroepithelial HSV-1 infection also elicited no significant AFC response in the NALT and a weak IgA response. Thus, olfactory herpesvirus infection differed immunologically from an infection of the adjacent respiratory epithelium. Poor IgA induction may help herpesviruses to transmit via long-term mucosal shedding. IMPORTANCEHerpesviruses are widespread, persistent pathogens against which vaccines have had limited success. We need to understand better how they interact with host immunity. MuHV-4 and HSV-1 inhaled by alert mice infect the olfactory neuroepithelium, suggesting that this is a natural entry route. Its immunology is almost completely unknown. The antibody response to neuroepithelial herpesvirus infection started in the cervical lymph nodes, and unlike respiratory influenza virus infection, did not significantly involve the nasal-associated lymphoid tissue. MuHV-4 and HSV-1 infections also elicited little virus-specific IgA. Therefore, vaccine-induced IgA might provide a defense that herpesviruses are ill-equipped to meet.

Seroconversion and Skin Mucosal Parameters during Koi Herpesvirus Shedding in Common Carp, Cyprinus carpio

“…Moreover, when the mucosal response of fish challenged at a permissive temperature of 17 °C was assessed, IgMsec was up-regulated in the survivors coinciding with the end of the shedding episode. Thus, the results suggest that a weak immunoglobulin induction might contribute to the long term mucosal shedding, similar to that described for murid herpesvirus 4 (MuHV-4) and herpes simplex virus 1 (HSV-1) in a mouse model [ 53 ], and that high concentration of IgMsec in the skin of common carp prevents further viral replication, similar to that observed for IgG concentration in mucus secretions during herpesvirus infections in humans [ 54 ].…”

Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

“…The antibody response to naturally transmitted virus clearly developed slower than that to experimental infection, presumably because the infectious dose was less. The antibody response to HCMV also develops slowly ( 30 ), as does that to inhaled MuHV-4 ( 31 ), suggesting that rapid responses to experimentally injected viruses might reflect dose and inoculation route more than species differences.…”

Rhadinovirus Host Entry by Co-operative Infection

“…Membrane fusion blocks or strong IgA responses might block host entry, because all infection requires fusion and mucosal IgA has a strong outward flux. However MuHV-4 elicits little post-binding neutralization [ 76 ] and little IgA [ 77 ]; antibody protects by effector recruitment [ 78 ] and poorly blocks host entry [ 59 ]. MuHV-4 is adapted to B cell physiology like EBV [ 79 ] but also to myeloid physiology, which encompasses the capture, transport and transfer of environmental antigens to B cells.…”