Pathogenesis

FPV causes a systemic infection. The virus is transmitted via the faecal-oral route, initially replicates in tissues of the oropharynx and is then distributed via cell-free viraemia to virtually all tissues. Replication of the parvovirus with its single-stranded DNA genome requires cells in the S-phase of division and is therefore restricted to mitotically active tissues. The reason for this is that parvoviruses require cellular DNA polymerases that synthesize the complementary DNA strand, which is the first step in viral DNA replication and a prerequisite for transcription.
The virus readily infects lymphoid tissues and can cause cellular depletion and a functional immunosuppression. Lymphopenia may arise as a result of lymphocytolysis but may also result from indirect effects, such as lymphocyte migration into tissues. The bone marrow is also affected, and virus replication has been described in early progenitor cells, which may explain the dramatic effect on virtually all myeloid cell populations (Parrish, 1995). This is also reflected by the defining panleukopenia observed in FPV infected cats (Truyen and Parrish, 2000).
The hallmark of FPV replication is the shortening of the intestinal villi due to a sometimes complete loss of epithelial cells in the gut (Parrish 2006). The virus replicates in the rapidly dividing cells of the epithelium, the crypts of Lieberkühn. This impairs the regeneration of the epithelium and results in the lesions described above. The severity of these lesions appears to correlate with the turnover rate of these cells, and co-infection with enteric viruses like feline coronavirus may enhance the severity of disease.
Intrauterine transmission or perinatal infection may affect the central nervous system. A feline ataxia syndrome has been described that results from an impaired development of the cerebellum due to lytic virus replication in the Purkinje cells in the infected kitten (Csiza et al., 1971; Kilham et al., 1971). An FPV-like virus has been described as the cause of reproductive disorders in pregnant foxes (Veijalainen and Smeds, 1988).

Immunopathogenesis of FPV infection

Foetal infection may induce a form of immunological tolerance so that kittens continue to shed virus for extended periods of time after birth (Pedersen, 1987).
Foetuses infected between the 35th and 45th days of gestation have depressed T-lymphocyte mediated immunity. Infection of adult cats leads to a transient decrease in the immune response. Neutrophils decrease severely and lymphocytes disappear from the circulation, lymph nodes, bone marrow and thymus (Ikeda et al., 1998; Pedersen, 1987).

Table 1.1. Pathological consequences and clinical manifestations of FPV infection

Affected cells	Consequences	Clinical manifestation
Intestinal crypt epithelium	Villous collapse, enteritis	Diarrhoea
Lymph node, thymus	Germinal centre depletion, apoptosis of lymphocytes, thymic atrophy	Lymphopenia
Bone marrow	Stem cell depletion	Neutropenia (later also thrombocytopenia and anaemia)
All cells in foetus	Foetal death	Loss of pregnancy
Developing cerebellum	Cerebellar hypoplasia	Cerebellar ataxia

Adapted from: Chandler, Feline Medicine and Therapeutics, 3rd Ed, 2004.

Passive immunity acquired via colostrum

Maternal antibodies have a biological half-life of about ten days (Scott et al., 1970; Pedersen
1987). Waning antibodies below a titre of about 40 (haemagglutination inhibition) do not
reliably protect against infection but may interfere with active immunization. Most cats have
maternal antibodies at protective titres until weeks 6 to 8. However, the effectiveness of later
vaccinations was demonstrated (Dawson et al., 2001), which supports the recommendation by
ABCD of vaccinations at 15 to 16 weeks of age, as explained in the present Guidelines.

Since the endotheliochorial placentation of the cat restricts maternofetal passage of solutes, IgG can only cross the placenta barrier in the last trimester of gestation. This passive immunity affords <10 % of the kitten’s maternal immunity. Therefore, ingesting sufficient colostrum is essential for acquiring protective levels of neutralising antibodies from the queen. Maximum absorption is around the 8th hour of life. Later, the kitten’s intestinal cells are replaced by new cells that can no longer absorb and transport antibodies.
Kitten serum antibody titres are generally equivalent to 50 % of those of the dam. However, the antibody level is also dependent on the individual colostrum intake. This explains the large variations between littermates (Casseleux and Fontaine, 2006). The antibody titres decrease in the first weeks of life, by decay and by dilution in the growing organism. By analogy with canine parvovirus, an immunity gap around 6 to 8 weeks of age is assumed to exist, when antibody levels are too low to protect against natural infection, but still high enough to interfere with vaccination ( Scott et al., 1970; Dawson et al., 2001; Thiry, 2002b).

Active immune response against FPV

Antibodies play an important role in the immune response to FPV. Maternally-derived antibodies (MDA) efficiently protect kittens from fatal infection. This passively acquired immunity is later replaced by an active immune response obtained by vaccination or as a consequence of natural infections.
Acquired immunity is solid and long lasting (Thiry, 2002a). Both inactivated and modified live virus (MLV) vaccines induce durable immunity. FPV antiserum can be used for passive immunisation when unvaccinated animal are likely to be exposed to virus before the initiation of a vaccine-induced, active response (Barlough et al., 1997).
Parvoviruses induce a range of immune responses including T-helper CD4+ lymphocytes and CD8+ cytotoxic T lymphocytes. The cellular response against the VP2 parvovirus capsid protein is mediated by CD4+ and CD8+ T lymphocytes in the context of the Major Histocompatibility Complex type II, as evidenced by the production of interleukin 2 by T lymphocytes stimulated with CPV2 (Rimmelzwaan et al., 1990). Parvovirus can be captured by phagocytosis but also by other non-phagocytic uptake mechanisms such as fluid pinocytosis or receptor-mediated endocytosis (Sedlik et al., 2000).

Previous Next