Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis

Abstract

Canine distemper virus (CDV), a negative stranded RNA morbillivirus, causes a multisystemic disease in dogs, which is associated with a severe immune suppression. The aim of the study was to examine the influence of early CDV infection on leukocyte depletion, lymphopenia and virus-induced cell death in dogs infected with a virulent CDV strain. From 10 infected dogs, peripheral blood leukocytes were harvested periodically, phenotyped and analyzed for CDV antigen content and apoptosis using Annexin V-FITC and propidium iodide labeling. CDV infection induced a severe CD3+ T cell and CD21+ B cell depletion in all animals at 3 days post-infection (d.p.i.). For dogs with severe distemper, developing virus persistence in the lymphoid tissue and central nervous system, this lymphopenia lasted until the end of the experiment. Increased levels of lymphocyte apoptosis were found at 3 d.p.i., and monocyte apoptosis at 6 d.p.i. This was more prominent in the group of animals with severe distemper. At 3 d.p.i. no leukocyte infection was detectable indicating that the early lymphocyte depletion and apoptosis was not a direct consequence of virus infection. Taken together, our results demonstrate that CDV-induced lymphopenia is an early event and that the degree of lymphocyte depletion correlates with the severity of disease and virus persistence in the lymphoid tissue and central nervous system.

Distribution of Inclusion Bodies in Tissues from 100 Dogs Infected with Canine Distemper Virus

“…Therefore, CDV can be detected in tonsils at an early stage [1,8]. CDV infection in dogs induces marked depletion of lymphocytes in both T-and B-cell dependent areas of the lymphoid tissues in the early stages of infection, as is the case for other morbillivirus infections, such as measles and rinderpest [3,6,7]. In fact, previous studies support the above process of infection [1,4], and abundant CDV antigen is most frequently detected from the early to late stages of infection in lymphoid organs, especially the tonsils [8].…”

Alterações citológicas do sangue periférico e da medula óssea de cães com cinomose

“…Outros trabalhos descreveram linfopenia em cães com CC (Moro, 2001;Schobesberger et al, 2005). Segundo Jain (1993), a linfopenia está relacionada com atrofia e necrose de tecido linfoide produzida pela ação do vírus.…”

Immunohistochemical detection of metalloproteinase-9 (MMP-9), anti-oxidant like 1 protein (AOP-1) and synaptosomal-associated protein (SNAP-25) in the cerebella of dogs naturally infected with spontaneous canine distemper

“…Demyelinating distemper leukoencephalitis (DL) represents the primary outcome in dogs. Due to the morphology of the neuropathological changes, this disease has come to be regarded as an important spontaneously occurring animal model of human demyelinating disease that is analogous to multiple sclerosis (MS) [2][3][4]. Initiation of demyelination has been described as a direct viral action, during which plaque progression seems to be mediated by this interaction [4].…”

“…Initiation of demyelination has been described as a direct viral action, during which plaque progression seems to be mediated by this interaction [4]. During the initiation phase, viral proteins, mRNAs, major histocompatibility complex class II, hyaluronate receptor CD44 and pro-inflammatory cytokines are increased [1][2][3][4][5][6][7]. In contrast, chronic lesions are characterized by the reduction or loss of viral proteins and mRNA, a strong MHC II upregulation and a massive influx of monocytes [5].…”