Oral Inoculation of Specific-Pathogen-Free Chickens with Chicken Anemia Virus Induces Dose-Dependent Viremia and Transient Anemia

Abstract

Chicken infectious anemia caused by chicken anemia virus (CAV) is a very important immunosuppressive disease in chickens. The horizontal spread of CAV in field chickens has been confirmed mainly through oral infection in our published article. Anemia is the main symptom of this disease. Studies by other scientists have shown that infection of CAV in 1-day-old chicks can cause anemia, and the degree of anemia is directly proportional to the dose of infectious virus. However, the pathogenesis of oral inoculation of CAV in older chickens is still not well understood. The purpose of this study was to determine whether 3-weeks-old specific-pathogen-free (SPF) chickens infected with different viral doses in oral route would cause anemia, as well as other signs associated with age-resistance. The experimental design was divided into a high-dose inoculated group (106 1050), low-dose inoculated group (103 TCID50), and non-virus inoculated control group, and 12 birds in each group at the beginning of the trial. The packed cell volumes (PCVs), CAV genome copies in tissues, CAV titer in peripheral blood fractions, and serology were evaluated at 7, 14, and 21 days post-infection (dpi). Virus replication and spread were estimated using quantitative polymerase chain reaction (qPCR) and viral titration in cell culture, respectively. The results showed that the average PCVs value of the high-dose inoculated group was significantly lower than that of the control group at 14 dpi (p < 0.05), and 44.4% (4/9) of the chickens reached the anemia level (PCVs < 27%). At 21 dpi, the average PCV value rebounded but remained lower than the control group without significant differences. In the low-dose inoculated group, all birds did not reach anemia during the entire trial period. Peripheral blood analysis showed that the virus titer in all erythrocyte, granulocyte and mononuclear cell reached the peak at 14 dpi regardless of the high-dose or low-dose inoculated group, and the highest virus titer appeared in the high-dose inoculated group of mononuclear cell. In the low-dose inoculated group, CAV was detected only at 14 dpi in erythrocyte. Taken together, our results indicate that the older birds require a higher dose of infectious CAV to cause anemia after about 14 days of infection, which is related to apoptosis caused by viral infection of erythrocytes. In both inoculated groups, the viral genome copies did not increase in the bone marrow, which indicated that minimal cell susceptibility to CAV was found in older chickens. In the low-dose inoculated group, only mononuclear cells can still be detected with CAV at 21 dpi in seropositive chickens, indicating that the mononuclear cell is the target cell for persistent infection. Therefore, complete elimination of the CAV may still require the aid of a cell-mediated immune response (CMI), although it has previously been reported to be inhibited by CAV infection. Prevention of early exposure to CAV could be possible by improved hygiene procedures.

Genomic Sequence and Pathogenicity of the Chicken Anemia Virus Isolated From Chicken in Yunnan Province, China

“…Besides, CAV was positive in each detected tissue organ from 7 to 21 dpi. Moreover, our study found that the viral load in thymus was highest in the infection group compared with other organ tissues ( 16 , 22 ). The above results suggested that CAV is highly susceptible to infection of central immune organs including thymus and bursa.…”

“…Furthermore, marked changes were also observed in the hematological parameters and histopathological changes at 14 dpi. Specifically, there was a significant decrease in the PCV of infected chickens at 14 dpi ( 22 ). Severe atrophy of thymus and bursa, mild to moderate atrophy of spleen, and pale bone marrow were observed in infected chickens at 14 dpi.…”

“…CIA is an extremely epidemic immunosuppressive disease in young chickens, which is characterized by severe anemia, weight loss, aplasia of bone marrow, and generalized lymphoid atrophy with concomitant immunosuppression ( 20 ). CAV can spread both horizontally and vertically ( 21 , 22 ). In adult birds, the virus serves as an important cofactor for establishment of other viral infections, such as Marek's Disease virus (MDV), reticuloendotheliosis virus (REV), infectious bursal disease virus (IBDV), avian leukosis virus subgroup J (ALV-J), reovirus, and adenovirus ( 23 , 24 ).…”

Genetic Differences and Pathogenicity of Chicken Anemia Virus Strains in Broiler’s Baby Chicks

“…The hematological profile of the infected groups showed hypochromic anemia characterized by a decrease in PCV, erythrocyte count, and hemoglobin content, which could potentially be attributed to the direct link to the virus's direct effect on the bone marrow, resulting in aplasia and a detrimental impact on the erythrocytic and granulocytic lineages of bone marrow cells, consequently affecting erythropoiesis and myelopoiesis [34]. The leukocytic finding of infected groups showed leukocytopenia, which could be attributed to the fact that the primary cells affected during CAV infection's progression involve hematopoietic progenitor cells in the bone marrow and thymic precursor cells in the thymus cortex [35].…”

Genetic characterization of chicken infectious anaemia viruses isolated in Korea and their pathogenicity in chicks

“…Previous studies have reported that lymphoid tissues are the primary targets for CIAV infection, and CIAV persists in thymic lymphocytes where it cannot be neutralized by the antibody ( Cardona et al., 2000 ; Markowski-Grimsrud and Schat, 2003 ; Tongkamsai et al., 2019a ). Continuous dissemination of the virus from the thymus with insufficient antibody response and the release of infected cells from the thymus into blood circulation might be the cause for the increased virus distribution in the other tissues ( Tongkamsai et al., 2019b ). Subsequently, CIAV can be replicated in the secondary tissues, and transmitted through horizontal contact or vertical transmission via hatching eggs.…”