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HIVirus co-infection in Africa: Our experience in South Africa and Sudan
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Abstracts / Journal of Clinical Virology 69 (2015) 223–246
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NOD1 ligand modulates the course of hepatitis B virus infection in hydrodynamic injection mouse model
Hepatitis B virus/HIVirus co-infection in Africa: Our experience in South Africa and Sudan
S. Huang 1,∗ , M. Chen 1 , X. Zhao 1 , Y. Xia 1 , C. Sun 1 , Y. Lin 1 , B. Wang 1 , X. Zheng 1 , M. Lu 2 , D. Yang 1 , J. Wu 1 1 Department of Infectious Disease, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China 2 Department of Virology, University Hospital of Essen, Essen, Germany
Background: Increasing evidence suggests that pattern recognition receptor (PRR) agonists could be used as immunomodulatory agents to control viral infection. We addressed the questions whether NOD1 or NOD2 ligand induces hepatitis B virus (HBV) clearance in a hydrodynamic injection (HI) mouse model. Methods: HI of pAAV/HBV1.2 in C57BL/6 mice leads to a transient HBV gene expression and replication in the liver. Different doses of NOD1/NOD2 ligand or NS were administered by HI or intraperitoneally (IP) or intramuscularly (IM) 14 day post pAAV/HBV1.2 injection. Serological markers of HBV infection were assayed at the indicated time points by ELISA. Serum HBV DNA was quantified by real time PCR. CD molecules and cytokine mRNAs in mouse liver tissues were detected by real-time RT-PCR. Liver tissue sections were stained with anti-HBc antibodies. The frequencies of antigen-specific interferon ␥ secreting splenocytes were measured by using ELISPOT assay. Findings: Only doses of 20 g NOD1 ligand delivered by HI significantly reduced HBsAg and HBV DNA levels in the animals. By contrast, the serum HBsAg and HBeAg levels in mice receiving NOD1 ligand by IP or IM injection or in mice receiving NOD2 ligand by HI, IP, or IM injection were not reduced compared with those receiving the NS control. The numbers of HBcAg positive hepatocytes were decreased by NOD1 treatment, compared with those in the NS group. The levels of CD3/CD4/CD8/perforin/IL6/CXCL2/CCL5 mRNAs were higher in liver of NOD1 ligand-treated mice when compared with those of control mice. The frequencies of antigenspecific interferon ␥ secreting cells were higher in the NOD1 ligand-treated mice. Interpretation: NOD1 ligand inhibits HBV replication in C57BL/6 mice when injected by HI, primarily due to the enhancement of a T cell response, implicating the potential of NOD1 activation for the treatment of chronic hepatitis B patients. http://dx.doi.org/10.1016/j.jcv.2015.06.043
A. Kramvis 1,∗ , T.G. Bell 1 , E. Makondo 1 , M. Yousif 1 , H. Mudawi 2 , D. Glebe 3 1
Hepatitis Virus Diversity Research Programme, University of the Witwtarsrand, Johannesburg, South Africa 2 Department of Medicine, Faculty of Medicine, University of Khartoum, Sudan 3 Institute of Medical Virology, National Reference Centre of Hepatitis B and D, Justus Liebig-University of Giessen, Giessen, Germany Background: Of the 34 million people infected with HIV globally, 22 million reside in Africa, and there is a correspondingly high prevalence of hepatitis B virus (HBV) infection. Morbidity and mortality attributed to HBV-associated end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC), can be exacerbated by HIV infection. The aim of our studies was to determine the prevalence of HBV/HIV coinfection. Methods: We cross-sectionally studied HBV/HIV co-infection in 298 adults in South Africa and in 358 adults in Sudan. Findings: In the South African study, we found that the only factor differentiating HBV DNA-positive from HBV DNAnegative HIV-infected individuals was the number of lifetime sexual partners, implicating sexual transmission. HBV infection was predominantly HBsAg-negative, which did not differ significantly from HBsAg-positive infection in terms of viral loads, CD4 counts, and ALT levels. HIV-infected South Africans were predominantly infected with subgenotype A1 of HBV. HBV from HIV-infected individuals had pre-S deletion mutations identical to those isolated from HCC patients. 10% of patients had HBV with drug resistance mutations before initiation of antiretroviral therapy. In the Sudanese study, intravenous drug use was a risk factor for HBV exposure in HIV-infected individuals, with iatrogenic transmission and advanced AIDS being additional risk factors. HBV infection was predominantly HBsAg-negative, with HBsAg-positive individuals having higher HBV viral loads. HIV-infected Sudanese were infected with genotype D or E, with genotype A and D/E recombinants occurring at a higher frequency compared to HBV mono-infected individuals. Interpretation: HBV/HIV co-infection is frequent in Africa, with approximately 25% of HIV-infected individuals being co-infected with HBV, the majority of whom are HBsAg-negative. HBsAg serology underestimates the presence of HBV in HIV-infected individuals. Moreover, different genotypes were found to circulate in South Africa and Sudan, and these may have a role in differences in clinical manifestation of HBV/HIV co-infection. http://dx.doi.org/10.1016/j.jcv.2015.06.044
Abstracts / Journal of Clinical Virology 69 (2015) 223–246
P0036
P0037
NOD1 ligand modulates the course of hepatitis B virus infection in hydrodynamic injection mouse model
Hepatitis B virus/HIVirus co-infection in Africa: Our experience in South Africa and Sudan
S. Huang 1,∗ , M. Chen 1 , X. Zhao 1 , Y. Xia 1 , C. Sun 1 , Y. Lin 1 , B. Wang 1 , X. Zheng 1 , M. Lu 2 , D. Yang 1 , J. Wu 1 1 Department of Infectious Disease, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China 2 Department of Virology, University Hospital of Essen, Essen, Germany
Background: Increasing evidence suggests that pattern recognition receptor (PRR) agonists could be used as immunomodulatory agents to control viral infection. We addressed the questions whether NOD1 or NOD2 ligand induces hepatitis B virus (HBV) clearance in a hydrodynamic injection (HI) mouse model. Methods: HI of pAAV/HBV1.2 in C57BL/6 mice leads to a transient HBV gene expression and replication in the liver. Different doses of NOD1/NOD2 ligand or NS were administered by HI or intraperitoneally (IP) or intramuscularly (IM) 14 day post pAAV/HBV1.2 injection. Serological markers of HBV infection were assayed at the indicated time points by ELISA. Serum HBV DNA was quantified by real time PCR. CD molecules and cytokine mRNAs in mouse liver tissues were detected by real-time RT-PCR. Liver tissue sections were stained with anti-HBc antibodies. The frequencies of antigen-specific interferon ␥ secreting splenocytes were measured by using ELISPOT assay. Findings: Only doses of 20 g NOD1 ligand delivered by HI significantly reduced HBsAg and HBV DNA levels in the animals. By contrast, the serum HBsAg and HBeAg levels in mice receiving NOD1 ligand by IP or IM injection or in mice receiving NOD2 ligand by HI, IP, or IM injection were not reduced compared with those receiving the NS control. The numbers of HBcAg positive hepatocytes were decreased by NOD1 treatment, compared with those in the NS group. The levels of CD3/CD4/CD8/perforin/IL6/CXCL2/CCL5 mRNAs were higher in liver of NOD1 ligand-treated mice when compared with those of control mice. The frequencies of antigenspecific interferon ␥ secreting cells were higher in the NOD1 ligand-treated mice. Interpretation: NOD1 ligand inhibits HBV replication in C57BL/6 mice when injected by HI, primarily due to the enhancement of a T cell response, implicating the potential of NOD1 activation for the treatment of chronic hepatitis B patients. http://dx.doi.org/10.1016/j.jcv.2015.06.043
A. Kramvis 1,∗ , T.G. Bell 1 , E. Makondo 1 , M. Yousif 1 , H. Mudawi 2 , D. Glebe 3 1
Hepatitis Virus Diversity Research Programme, University of the Witwtarsrand, Johannesburg, South Africa 2 Department of Medicine, Faculty of Medicine, University of Khartoum, Sudan 3 Institute of Medical Virology, National Reference Centre of Hepatitis B and D, Justus Liebig-University of Giessen, Giessen, Germany Background: Of the 34 million people infected with HIV globally, 22 million reside in Africa, and there is a correspondingly high prevalence of hepatitis B virus (HBV) infection. Morbidity and mortality attributed to HBV-associated end-stage liver disease, including cirrhosis and hepatocellular carcinoma (HCC), can be exacerbated by HIV infection. The aim of our studies was to determine the prevalence of HBV/HIV coinfection. Methods: We cross-sectionally studied HBV/HIV co-infection in 298 adults in South Africa and in 358 adults in Sudan. Findings: In the South African study, we found that the only factor differentiating HBV DNA-positive from HBV DNAnegative HIV-infected individuals was the number of lifetime sexual partners, implicating sexual transmission. HBV infection was predominantly HBsAg-negative, which did not differ significantly from HBsAg-positive infection in terms of viral loads, CD4 counts, and ALT levels. HIV-infected South Africans were predominantly infected with subgenotype A1 of HBV. HBV from HIV-infected individuals had pre-S deletion mutations identical to those isolated from HCC patients. 10% of patients had HBV with drug resistance mutations before initiation of antiretroviral therapy. In the Sudanese study, intravenous drug use was a risk factor for HBV exposure in HIV-infected individuals, with iatrogenic transmission and advanced AIDS being additional risk factors. HBV infection was predominantly HBsAg-negative, with HBsAg-positive individuals having higher HBV viral loads. HIV-infected Sudanese were infected with genotype D or E, with genotype A and D/E recombinants occurring at a higher frequency compared to HBV mono-infected individuals. Interpretation: HBV/HIV co-infection is frequent in Africa, with approximately 25% of HIV-infected individuals being co-infected with HBV, the majority of whom are HBsAg-negative. HBsAg serology underestimates the presence of HBV in HIV-infected individuals. Moreover, different genotypes were found to circulate in South Africa and Sudan, and these may have a role in differences in clinical manifestation of HBV/HIV co-infection. http://dx.doi.org/10.1016/j.jcv.2015.06.044