The Foot-and-Mouth Disease Carrier State Divergence in Cattle

Abstract

The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis.IMPORTANCE The existence of a prolonged, asymptomatic carrier state is a political impediment for control and potential eradication of foot-and-mouth disease (FMD). When FMD outbreaks occur, they are often extinguished by massive depopulation of livestock due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty over the biological relevance of FMD virus (FMDV) persistence. The work described here elucidates aspects of the FMDV carrier state in cattle which may facilitate identification and/or abrogation of asymptomatic FMDV infection. The divergence between animals that clear infection and those that develop persistent infection was demonstrated to occur earlier than previously established. The host antiviral response in tissues maintaining persistent FMDV was downregulated, whereas upregulation of IFN-λ mRNA was found in the epithelium of cattle that had recently cleared the infection. This suggests that the clearing of FMDV infection is associated with an enhanced mucosal antiviral response, whereas FMDV persistence...

Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

“…This is consistent with previous works which have localized FMDV to these tissues in adult cows using immunomicroscopy [14, 15, 47] or in situ hybridization [50, 59–61]. The current localization of FMDV to subepithelial regions of the soft palate differs from previous descriptions in adult cattle.…”

“…In order to assess the causality of abortion and potential of vertical/transplacental transmission of FMDV from infected cows to fetuses, eight aborted calves from affected farms were selected and each was screened by post mortem examination. Although recent works have elucidated several aspects of FMDV pathogenesis in adult cattle [14, 15, 45–47], there are no reports regarding the pathological lesions or presence of viral genome in fetal tissues aborted from FMDV-infected cows. Additionally, there is no previous documentation of FMDV inducing abortion in cattle under experimental or field conditions.…”

“…Previous studies have demonstrated that the dorsal soft palate and the dorsal nasopharynx (the floor and ceiling of the nasopharynx, respectively) is a site of unique FMDV-host tropism in adult cattle during the early [14, 15, 48] and persistent [46, 47, 49, 50] stages of FMD pathogenesis. Earlier works have demonstrated detection of viral RNA for up to two days after cessation of viremia in numerous tissues, but substantially longer duration of detection (up to 72 dpi) in pharyngeal tissues and lymph nodes [47, 51]. In the calves described herein, viral RNA was also detected in the submandibular lymph node (2/8 cases) which is consistent with previous work demonstrating FMDV antigens in lymph nodes of cattle during persistent infection [52].…”

“…Several works have contributed to the growing understanding of the unique tropism of FMDV for the bovine nasopharynx during the acute [14, 15, 48] and persistent phase [46, 47, 49, 50] of infection. Microscopic localization of FMDV antigen has been demonstrated within the superficial epithelium of the nasopharynx of cattle [14, 15, 46, 47]. Similarly, FMDV RNA has been localized in the basal layers of the epithelium of the dorsal soft palate and pharynx [50, 61].…”

Quantitative characteristics of the foot‐and‐mouth disease carrier state under natural conditions in India

“…Additionally, a variable proportion of animals in a herd may be subclinically infected and do not show any clinical signs of infection. This phenomenon is most common amongst vaccinated animals (McVicar & Sutmoller, ; Parthiban, Mahapatra, Gubbins, & Parida, ; Stenfeldt, Eschbaumer et al., ). In some clinically and subclinically infected ruminants, FMDV can be isolated from oropharyngeal fluids and/or tissues >28 days after infection.…”