Similar patterns of infection with bovine foamy virus in experimentally inoculated calves and sheep

Abstract

Foamy viruses (FVs) are the least known retroviruses commonly found in primates, cats, horses, and cattle. Although FVs are considered apathogenic, simian and feline FVs have been shown to be associated with some transient health abnormalities in animal models. Currently, data regarding the course of infection with bovine FV (BFV) are not available. In this study, we conducted experimental infections of natural (cattle) and heterologous (sheep) hosts with the BFV(100) isolate and monitored infection patterns in both hosts during the early phase postinoculation as well as after long-term infection. Four calves and six sheep inoculated with BFV(100) showed no signs of pathology but developed persistent infection, as confirmed by virus rescue, consistent detection of BFV-specific antibodies, and presence of viral DNA. In both hosts, antibodies against BFV Gag and Bet appeared early after infection and persisted at high and stable levels while seroreactivity toward Env was consistently detectable only in BFV-infected sheep. Interestingly, the BFV proviral DNA load was highest in lung, spleen, and liver and moderate in leukocytes, while salivary glands contained either low or undetectable DNA loads in calves or sheep, respectively. Additionally, comparison of partial BFV sequences from inoculum and infected animals demonstrated very limited changes after long-term infection in the heterologous host, clearly less than those found in BFV field isolates. The persistence of BFV infection in both hosts suggests full replication competence of the BFV(100) isolate with no requirement of genetic adaptation for productive replication in the authentic and even in a heterologous host.

Fig 1

Detection of BFV Gag protein in cocultures by indirect immunofluorescence. Cf2Th cells cocultivated with PBLs of sheep 3 (A) and uninfected Cf2Th cells (B). Indirect immunofluorescence was done using rabbit BFV Gag-specific antiserum and anti-rabbit-Alexa-488. Nuclei were stained with Hoechst 33342.

Fig 2

Seroreactivity to BFV proteins in calves and sheep at the early stage of infection. The humoral response to BFV antigens was tested by GST ELISA during the first 12 weeks p.i. in four calves experimentally inoculated with Cf2Th/BFV₁₀₀ (A) and in four sheep inoculated with blood of two donor sheep (B). Background-subtracted OD₄₅₀ values are given.

Fig 3

Seroreactivity to BFV proteins in calves, sheep, and cows upon euthanasia/slaughtering. The humoral response to BFV antigens was tested by GST ELISA at 5 months p.i. in four calves inoculated with Cf2Th/BFV₁₀₀ (A) and in four cows naturally infected with BFV (B) and at 36 months p.i. in two donor sheep inoculated with Cf2Th/BFV₁₀₀ (C) and four sheep inoculated with the blood of two donor sheep (D). Background-subtracted OD₄₅₀ values are given.

Fig 4

BFV DNA load in PBLs of calves and sheep at the early phase of infection. The load of BFV DNA was determined by qPCR in PBLs of four calves experimentally inoculated with Cf2Th/BFV₁₀₀ (A) and four sheep experimentally inoculated with blood of donor sheep (B) during the first 12 weeks p.i. Note that different scales to present the BFV DNA copy numbers have been used in the two panels.

Fig 5

BFV DNA load in tissues of claves, sheep, and cows. The load of BFV DNA was determined by qPCR at the end of experiment in organs of four calves experimentally inoculated with Cf2Th/BFV₁₀₀ (A), four sheep experimentally inoculated with the blood of donor sheep (B), four cows naturally infected with BFV (C), and two donor sheep experimentally inoculated with Cf2Th/BFV₁₀₀ (D). Note that different scales to present the BFV DNA copy numbers have been used in the graphs.