Mouse hepatitis virus and host determinants of vertical transmission and maternally-derived passive immunity in mice (original) (raw)
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Transmission of enterotropic mouse hepatitis virus from immunocompetent and immunodeficient mice
Mouse hepatitis virus (MHV) is the most prevalent virus that infects laboratory mice (31), and is a major concern in laboratory animal facilities because of its potential to disrupt mouse-based immunologic and oncologic research by interfering with biological responses and through clinical illness and mortality. Infection with MHV has been documented to alter tumor growth, invasion patterns, regression, and oncolysis . Disruption of immunologic research is linked to the ability of MHV to alter normative responses through viral replication in T and B lymphocytes and macrophages (3, 20, 34). Infection with MHV can alter peritoneal macrophage function, impair dendritic and/ or T-cell function in Peyer's patches, suppress splenic CD8 + T-cell functions, alter cytokine production, impair antigen processing, and decrease rejection of skin allografts (9, 13, 18-22, 33, 45, 48).
Virology Journal, 2015
Background: Pregnant women from developing countries are at high-risk of hepatitis E-associated high mortality and constitute priority population for vaccination. So far, candidate vaccines have not been evaluated during pregnancy. We evaluated our vaccine candidate, recombinant Neutralizing Epitope protein (rNEp) encapsulated in liposomes, in pregnant mice. Methods: A single dose (10 μg) of the formulation was administered intramuscularly on day 7 of pregnancy. Titres of serum IgG antibodies to hepatitis E virus (IgG-anti-HEV), levels of cytokines and biochemical parameters were determined. Spleens were harvested from pregnant and non-pregnant mice for immunophenotyping (flow cytometry), cytokines (cytometric bead array, CBA) and gene expression of immune response genes (Taqman low density array, TLDA). Histopathology studies of spleen, liver, kidneys, brain and muscle was carried out. Results: The vaccine was well-tolerated during pregnancy as evidenced by histopathology and serum biochemical parameters. Anti-HEV titres were significantly higher in the pregnant balb/c and C57BL/6 mice (3592 ± 802 and1016 ± 138 respectively, than in non-pregnant groups (634 ± 191 and 320 ± 55 respectively, p < 0.001 for both) suggesting that the higher antibody response in pregnant mice was independent of the genetic makeup of the host but immunogen-driven. Pups receiving vertically transferred antibodies developed lower anti-HEV antibodies (p < 0.05) when immunized with the formulation after seronegativity than in the age-matched mice without such antibodies. In non-pregnant mice, a Th1 response and discordance between splenic and serum cytokines was evident while in pregnancy, a Th2 bias was observed irrespective of immunization. Increased CD19 levels correlated with higher anti-HEV titres in pregnant mice. Conclusion: The single dose of the vaccine was safe and highly immunogenic in pregnant mice. Degree and type of immune response to vaccination during pregnancy is immunogen-driven. In-depth studies are needed to understand the underlying immunologic mechanism(s). These encouraging results for a vaccine intended for use in pregnant women should be confirmed in higher animals.
Hepatitis C — Role of Perinatal Transmission
The Australian and New Zealand Journal of Obstetrics and Gynaecology, 1998
To evaluate the role of perinatal transmission in the spread of hepatitis C virus (HCV), we screened a cohort of pregnant intravenous drug using (IVDU) women for HCV antibody detection; where seropositive HCV RNA detection by polymerase chain reaction (PCR) was found we followed the infants longitudinally for HCV antibody and HCV RNA. Serum prevalence for HCV for this population was 80% with HCV RNA detected in 50%. Recruitment and follow-up over a 3year period of a cohort of 83 seropositive women, their 91 newborns and 16 siblings of newborns, showed that there had been a 3% perinatal transmission rate with 1 sibling also infected. These positive cases were defined as transient in 1 case (HCV RNA positive by PCR at 1 month, but seronegative and HCV RNA negative at 10 months of age), 2 unevaluable (HCV RNA positive at 2 months of age, but patients lost to follow-up), and 1 chronic infection in a child at 34 months (positive HCV RNA and seropositive 34-month sibling). Maternal HCV RNA levels for those with infected infants was a mean 40-fold greater than those whose babies were uninfected, although this did not reach statistical significance. Of the remaining infants, the majority (93%) had lost passively acquired maternal antibodies by 9 months of age and all by 12 months. Of 18 women who were HCV seropositive and breast feeding (66% of whom were HCV RNA positive in their sera), none had detectable HCV RNA in breast milk. Hence we conclude that transmission of HCV from mother to infant appears to be of low frequency and positivity appears to correlate with maternal circulating viral load.
Journal of Hepatology, 2020
5-fold increase in the HDV clearance rate is assumed after the reinoculation at 4 hr pi (Fig. 1 right). Conclusion: The unexpected biphasic early HDV kinetics observed in mice can be modeled by assuming the existence of a binding compartment with a constant off rate. The model predicts that HDV clearance is ∼5-fold enhanced after re-inoculation of HDV after 4 hr pi. However, further experiments and theoretical efforts are needed to formalize these results and predictions.
Perinatal transmission of hepatitis C antigens: envelope 1, envelope 2 and non-structural 4
Infectious Diseases, 2015
Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. we aimed to study the perinatal transmission of HCV structural and non-structural antigens. Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood. Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ElISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 0.01), E1 (0.86 0.01) and E2 (0.85 0.01) did not differ significantly (p 0.05) from those of neonatal cord blood (0.83 0.01, 0.87 0.01 and 0.85 0.01, respectively). Also, strong correlations (p 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r 0.77; E1, r 0.76 and E2, r 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p 0.05) from those in caesarean section. Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.
Maternal Immunity Influences Vertical Transmission of Hepatitis B to Newborns
Hepatology Communications, 2019
Vertical transmission of hepatitis B virus (HBV) from the mother to the newborn often results in viral persistence. To understand mechanisms of maternofetal HBV transmission, we studied maternal immunity and peripheral blood mononuclear cell (PBMC) transcriptome in mothers and newborns. We included 50 mothers and babies who were hepatitis B surface antigen (HBsAg) positive: 22 HBV transmitting mothers (group [Gr.] I) and 28 HBV nontransmitting mothers (Gr. II) to newborns and 10 healthy mother-baby pairs (Gr. III). PBMCs were analyzed for HBVspecific dendritic cells (DCs), T cells, T follicular helper (TFh) cells, B cells, functional immune responses, and cytokine levels as well as transcriptome signatures to identify immune gene expression correlates for protective immunity. Group II mothers had lower HBsAg levels (3.82 × 10 3 versus 1.493 × 10 4 ; P < 0.0001) with greater HBVspecific responses of DCs, T cells, TFh cells, and B cells than Gr. I mothers. Frequencies of TFh cells were lower in Gr. I mothers, with reduced interleukin-21 (IL-21) levels, and these inversely correlated with HBV DNA levels. Cutoff levels of 9.5% and 8.93% from the receiver operating curve predicted the involvement of TFh cells and B cells in HBV transmission. Transcriptome signatures revealed that maternal gene imprints were reflected in the newborns. Genes related to DCs, TFh cells, and B cells were increased in Gr. II, and Gr. II newborns showed a boost in cellular and humoral responses after vaccination. Conclusion: In mothers infected with HBV, low serum IL-21 levels and decreased TFh-cell and plasma B-cell frequencies are associated with vertical transmission of HBV to newborns. These features are indicative of low protective maternal immunity. (Hepatology Communications 2019;0:1-17).
Fetal Hepatic Response to Bovine Viral Diarrhea Virus Infection in Utero
Pathogens (Basel, Switzerland), 2018
Non-cytopathic bovine viral diarrhea virus (ncp BVDV) can cause persistent infection (PI) in animals infected in utero during early gestation. PI animals shed the virus for life and are the major source of the virus in herds. The mechanism responsible for BVDV immune tolerance in the PI fetus is unknown. We assessed the impact of BVDV infection on the fetal liver. Dams were inoculated with ncp BVDV at gestational day 75. Fetal liver samples were collected at necropsy, 7 and 14 days post-maternal-BVDV inoculation. BVDV antigen was not detected in the liver at gestational day 82 (7 days post-maternal inoculation). However, at 14 days post-maternal inoculation, BVDV was detected by immunohistochemistry in fetal Kupffer cells. Flow cytometry analysis showed a higher percentage of hepatic immune cells expressed MHC I and MHC II in BVDV-infected fetal liver (as compared to uninfected controls). Immunofluorescence was used to identify Kupffer cells, which were positive for BVDV antigen, ne...