Hepatitis E virus chronic infection of swine co-infected with Porcine Reproductive and Respiratory Syndrome Virus

Abstract

In developed countries, most of hepatitis E human cases are of zoonotic origin. Swine is a major hepatitis E virus (HEV) reservoir and foodborne transmissions after pork product consumption have been described. The risk for HEV-containing pig livers at slaughter time is related to the age at infection and to the virus shedding duration. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a virus that impairs the immune response; it is highly prevalent in pig production areas and suspected to influence HEV infection dynamics. The impact of PRRSV on the features of HEV infections was studied through an experimental HEV/PRRSV co-infection of specific-pathogen-free (SPF) pigs. The follow-up of the co-infected animals showed that HEV shedding was delayed by a factor of 1.9 in co-infected pigs compared to HEV-only infected pigs and specific immune response was delayed by a factor of 1.6. HEV shedding was significantly increased with co-infection and dramatically extended (48.6 versus 9.7 days for HEV only). The long-term HEV shedding was significantly correlated with the delayed humoral response in co-infected pigs. Direct transmission rate was estimated to be 4.7 times higher in case of co-infection than in HEV only infected pigs (0.70 and 0.15 per day respectively). HEV infection susceptibility was increased by a factor of 3.3, showing the major impact of PRRSV infection on HEV dynamics. Finally, HEV/PRRSV co-infection – frequently observed in pig herds – may lead to chronic HEV infection which may dramatically increase the risk of pig livers containing HEV at slaughter time.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0207-y) contains supplementary material, which is available to authorized users.

Natural viral co‐infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter

“… Exposure to co‐infecting pathogens: pig's status regarding PCV2 and PRRSV was recorded and pigs were categorized as PCV2 infected, PRRSV infected, or PCV2 and PRRSV infected, whatever the order of the infections. Sequence of co‐infections: First, ages at HEV/PCV2/PRRSV infection were calculated as followed: (1) pig's age at HEV infection was calculated as the age at HEV shedding minus 14 days, corresponding to HEV latency period as described in Salines et al (); (2) pig's age at PCV2 infection was calculated as the age at first PCV2 positive PCR minus 7 days, as described in literature (Andraud et al, , ); (3) similarly to the calculation of the age at HEV seroconversion, the age at PRRSV seroconversion was derived from the individual antibodies’ kinetics fitted with cubic splines; then, pig's age at PRRSV infection was calculated as the age at PRRSV seroconversion minus 7 days, as described in literature (Diaz, Darwich, Pappaterra, Pujols, & Mateu, ). Then, the sequence of infections was computed and four possible statuses were attributed to piglets: (i) infected by HEV first; (ii) infected by PCV2 first (i.e.…”

“…litter characteristics such as number of mummified, live‐born or weaned piglets, parity rank of the dam, maternal immunity) have not been investigated to date. Using mathematical modelling based either on experimental trials or on field studies revealed new insights on HEV infection dynamics (Andraud, Casas, Pavio, & Rose, ; Andraud et al, ; Salines et al, ). As such, a partial protection conferred by maternally derived antibodies (MDAs) was shown to delay HEV infection in growing pigs (Andraud et al, ).…”

“…Some compelling studies have shown yet that PRRSV infection could alter the immune response to viral infection or vaccination (Van Reeth, Nauwynck, & Pensaert, ; Suradhat et al, ). More specifically, PRRSV co‐infection is likely to lead to chronic HEV infection (Salines et al, ), with apparently extended latency and infectious period, increased HEV faecal shedding and impaired humoral immune response. Another swine virus, the porcine circovirus of type 2 (PCV2), is known to modulate the immune response as well.…”

From the epidemiology of hepatitis E virus (HEV) within the swine reservoir to public health risk mitigation strategies: a comprehensive review

“…For instance, a PRRSV/HEV co-infection or a PRRSV infection prior to HEV infection delayed HEV shedding and the onset of the anti-HEV humoral immune response, increased the quantity of virus particles shed and extended the shedding period, increased the direct transmission rate and HEV infection susceptibility, and increased the proportion of HEV-positive livers at slaughter time [33, 36]. Thus, controlling intercurrent swine diseases (e.g.…”

Prevalence and Phylogenetic Analysis of Hepatitis E Virus among Pigs in Japan

“…In short, once introduced into a farm, HEV is then present continuously there because of repeated transmission among susceptible herds, i.e., pigs without appropriate immunity. Recently, Salines et al (11) reported that experimental porcine reproductive and respiratory syndrome virus (PRRSV) and HEV coinfection affect the HEV infection dynamics in 5-week-old pigs in the absence of the maternal antibody against these 2 endemic viruses. The simultaneous coinfection resulted in a prolonged latent period and HEV shedding period as compared to pigs infected with HEV only.…”