The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper. Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Naïve cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection. Feline leukemia virus (FeLV) is a retrovirus of great veterinary importance that was discovered more than 40 years ago [20] and infects domestic cats and some related small felids worldwide [18, 22, 32] . An infection with FeLV may cause disorders of hematopoietic cells, a state of immunodeficiency and fatal neoplasia. Common symptoms are fever, anaemia, anorexia and weight loss. The prevalence of FeLV infection has been decreasing in the past few years. In Switzerland, FeLV prevalence was found to be 3% in healthy and of up to 13% in ill cats [29] . Decreasing prevalence is the consequence of identification and segregation of infected cats, and of extensive vaccination programs. However, cases of recurrence keep occurring and emphasise the importance of an accurate diagnosis [24] . FeLV is mainly transmitted directly from cat to cat. Transmission occurs through contact with saliva via licking, mutual grooming and sharing of food or water dishes or trough bites [5, 6] . Infectious FeLV can also be transmitted via faeces and milk [8, 34] . FeLV RNA was also detected in urine, but, its infection potential has not been demonstrated so far [1] . Pathogenesis is well understood if infectious pressure is high. Infection starts in the oropharynx where the virus first replicates in tonsils and local lymph nodes [37] , from which the virus spreads to the bone marrow, thymus, spleen and intestine through infected lymphocytes. Bone marrow infection is an important hallmark of FeLV pathogenesis as the virus replicates extensively in bone marrow and infects blood precursor cells first, and many organs and tissues thereafter, including salivary gland, tonsils, pharyngeal, urinary bladder, gastric, intestinal, colonic, pancreatic and endometrial epithelia, lymph nodes throughout the body, bone marrow, and spleen [36, 37] . FeLV infection presents a variety of outcomes [11, 16-18, 25, 27, 35, 37, 38] , which are influenced by both host and virus factors. Known host resistance factors include age and immune system status. Known virologic factors are virus strain, subtype and viral infection dose [18] . The outcome of infection is still a rather controversial issue. In the past, infection outcome was classified as viremic, non-viremic, and transiently viremic based on results of virus isolation, immunofluorescence assays and/or antigen detection [27] . Viremic cats are characterized by continuous expression of p27 viral antigen. FeLV infection is not contained due to a lack of FeLV specific immunity [3, 4, 18] . Viremic cats continuously shed virus, thereby posing a risk of infection to susceptible cats, and usually succumb to FeLV-associated diseases (anaemia, immunosuppression, and neoplasia). In transiently viremic cats, viremia is overcome after a few weeks post-infection (p.i.). However, transiently viremic cats remain provirus positive [15] . In addition, some nonviremic cats were shown to have localized infection characterized by virus replication in certain tissues, such as mammary, salivary and urinary epithelium [8, 12, 34] . This additional form of FeLV infection was termed atypical or sequestered infection. New sensitive molecular assays have been described recently for the use in detection and quantification of FeLV provirus DNA and viral RNA [14, 39, 42] , resulting in a more sensitive measure for FeLV exposure. The spectrum of host response categories was refined accordingly. Especially in p27 negative cats, the outcome should be reevaluated based on the presence or absence of FeLV proviral DNA in blood or bone marrow. The spectrum of host response categories was thus reclassified into: abortive (no virus detected after exposure), regressive (p27-negative, provirus positive after or without transient antigenemia) and progressive (persistently p27 positive, virus isolation, provirus positive, FeLV RNA positive) [16] . Whether cats that show no signs of infection (abortive) are truly immune or just resistant, is still open to debate. In this context, a very interesting finding was that FeLV infection can be transmitted by contact with faeces [8] with no apparent viremia and infection involving the bone marrow, and constant negativity for proviral DNA in blood -which would be classified as abortive infection. However, in the study of Gomes-Keller et al. [8] FeLV provirus could be detected in several organs and the cats showed seroconversion, indicating that infection indeed had occurred. It was concluded that under low infectious pressure a different pathogenesis may take place in which bone marrow is not involved. Since FeLV transmission at very low infection levels appears to be the most natural way of infection, many cats may show this yet uncharacterized outcome. Cats that test negative for FeLV by conventional diagnostic methods could still have been infected and constitute a relevant portion of the cat population affected by the virus. The prevalence of FeLV infection may therefore have been underestimated, a factor that can have important consequences for FeLV control management, e.g. in Iberian lynxes, which seem to be particularly susceptible for FeLV infection and for which a correct estimation of FeLV spreading potential is of great importance [32] . It was thus the aim of this study to further characterize the course of infection after exposure to low infectious pressure and to test the hypothesis that low FeLV doses applied to young cats may lead to seroconversion even when the infection does not progress through bone marrow. The virus may not be completely eliminated and a limited viral replication in tissues may lead to a development of a weak immune response. Three groups of 7 cats were exposed to different, low doses of FeLV. Blood p27 antigen, proviral DNA and viral RNA were measured in blood at regular intervals until week 20 p.i. and in popliteal and mesenteric lymph nodes, bone marrow, spleen, kidney, urinary bladder, lungs, thymus, myocardium, parotid gland, and pancreas after euthanasia. Immune response against FeLV was assessed by the detection of antibodies by ELISA to FeLV whole virus and to FeLV p45 (the recombinant env-gene product), by immunofluorescence assay to feline oncornavirus-associated cell membrane antigen (FOCMA), and by Western blot analysis to the separated FeLV components.