More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last dec...More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.展开更多
AIM： TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection （“anti-HBc alone”） among human immunodeficiency virus （HIV） type-1 infe...AIM： TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection （“anti-HBc alone”） among human immunodeficiency virus （HIV） type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS： Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus （HBV） infection were classified into three groups： past hepatitis, ＂anti-HBc alone＂ and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus （HCV） were performed on ＂anti-HBc alone＂ patients. RESULTS： One hundred and eighty seven （53.7%） HIV-positive patients had markers of HBV infection： 118 past infection （63.1%）, 14 chronic hepatitis （7.5%） and 55 ＂anti-HBc alone＂ （29.4%）. Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals （Cl） 1.33-4.00] and antibodies to HCV infection [odds ratio （OR） 2.87; 95% CI 1.10-7.48] were factors independently associated with the ＂anti-HBc alone＂ pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection （nor viral replication or HCV genotype）, or with HIV replication or CD4 level. No ＂anti-HBc alone＂ patient tested positive for HBV DNA. CONCLUSION： ＂Anti-HBc alone＂ prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,展开更多
Clinical observations have demonstrated that excessive chronic alcohol use negatively affects human immuno- deficiency virus (HIV) infection and contributes to the liver manifestations of the disease, even in HIV mono...Clinical observations have demonstrated that excessive chronic alcohol use negatively affects human immuno- deficiency virus (HIV) infection and contributes to the liver manifestations of the disease, even in HIV mono- infection. HIV/hepatitis C virus (HCV) co-infection is as- sociated with increased progression of HVC liver disease compared to HCV infection alone, and both of these are negatively affected by alcohol use. Recent data suggest that alcohol use and HIV infection have common targets that contribute to progression of liver disease. Both HIV infection and chronic alcohol use are associated with increased gut permeability and elevated plasma levels of lipopolysaccharide; a central activator of inflammatory responses. Both alcoholic liver disease and HIV infec tionresult in non-specific activation of innate immunity, proinflammatory cytokine cascade upregulation, as well as impaired antigen presenting cell and dendritic cell functions. Finally, alcohol, HIV and antiretroviral therapyaffect hepatocyte functions, which contributes to liver damage. The common targets of alcohol and HIV infection in liver disease are discussed in this minireview.展开更多
Squamous cell carcinoma of the anus （SCCA） is a com- mon cancer in the human immunodeficiency virus （HIV）- infected population, and its incidence continues to in- crease in male homosexuals. Combined chemoradiatio...Squamous cell carcinoma of the anus （SCCA） is a com- mon cancer in the human immunodeficiency virus （HIV）- infected population, and its incidence continues to in- crease in male homosexuals. Combined chemoradiation with mitomycin C and 5-fiuorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy （HAART）, however, recent data indicate that： （1） most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and （2） this approach is associ- ated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recur- rence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in mid- dle-aged HIV-positive male homosexuals. In this popula- tion, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses （HPVs）. Large-scale cancer-prevention strategies （routine anuscopy and anal papanicolaou test- ing） should be implemented in this population. In addi- tion, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination.展开更多
In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal di...In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule： a residual level hepatitis B virus （HBV） DNA at 24 wk predicts beneficial outcome and reduced resistance at i year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.展开更多
Objective: Allelic polymorphisms of CCR5△32CCR2b-64I,CX3CR1-2491280M and SDF1-3'A associatedwith HIV-1 infection and disease progression wereinvestigated in indigenous Uygur populations from theXinjiang Uygur Aut...Objective: Allelic polymorphisms of CCR5△32CCR2b-64I,CX3CR1-2491280M and SDF1-3'A associatedwith HIV-1 infection and disease progression wereinvestigated in indigenous Uygur populations from theXinjiang Uygur Autonomous Region of China. Methods: The study population comprised 316 healthyUygur subjects with an age range of 1-80 years old, fromwhom whole peripheral blood samples were collected andnone were HIV-1 seropositive. Genomic DNA samples werepurified using a Qiagen Blood Kit. Genotyping of theaforementioned four alleles was performed using PCR orPCR/RFLP assay, and further confirmed by direct DNAsequencing. Results: The allelic frequencies in Chinese Uygurpopulation were as follows: 3.48% for CCR5△32; 19.45% forCCR2b-64I; 13.8% for CX3CR1-2491280M haplotype, and20.41% for SDF1-3'A. Mutant allele distributions amongUygur populations were in accordance with theHardy-Weinberg equilibrium. No statistical difference wasfound between the frequency of the three HIV coreceptors andtheir respective ligand genes. Conclusion: The frequency of SDF1-3'A andCX3CR1-2491280M haplotypes in these Uygur populationswas similar to that of Caucasian people, while the frequency ofthe CCR2b-64I haplotype more closely matched the HanChinese. The frequency of CCR5△A32 in Uygur populationswas between Caucasian and Hall frequencies, the more closelymatching the frequency in Medi-Asia people. No geneticlinkage between any two of the three HIV coreceptor geneswas found, but obvious genetic linkages existed betweenCX3CR1-249I and CX3CR1-280M,with even higher linkagedegrees than Caucasian people.展开更多
Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 iso...Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 isolates, thus laying afoundation for designing a candidate AIDS vaccine. Methods: By hetero-duplex mobility assay (HMA) andsingle strand conformation poly-morphism (SSCP) analysison amplicons from single-primed polymerase chain reaction(SP-PCR), subtypes and quasi-species of tested HIV-1 isolateswere elucidated, and amplicons were sequenced forconfirmation. Results: Specific amplicons from different subtypes andquasi-species of HIV-1 could be discernible by HMA andSSCP analysis. Conclusion: HIV-1 isolates from different patients might beeither a different subtype or an identical subtype, and HIV-1isolates from an individual were present in a population ofquasi-species.展开更多
Human immunodeficiency virus type 1 （HIV-1）, a causative agent of AIDS, is affecting today more than 35 millions of people worldwide. The advance of anti-HIV chemotherapy has made AIDS a chronic non-fatal disease in...Human immunodeficiency virus type 1 （HIV-1）, a causative agent of AIDS, is affecting today more than 35 millions of people worldwide. The advance of anti-HIV chemotherapy has made AIDS a chronic non-fatal disease in resourceful countries. Longawaited anti-HIV-1 vaccine is still not with us yet; however, great progress in structural analyses of the envelope protein of HIV-1 in recent years starts to shed light on rational intervention targeted at the envelope protein, as will be reviewed in this article.展开更多
Human immunodeficiency virus （HIV） is a lenti-virus （a member of the retrovirus family） that causes acquired immunodeficieney syndrome （AIDS）, a critical condition in humans in which progressive failure of the i...Human immunodeficiency virus （HIV） is a lenti-virus （a member of the retrovirus family） that causes acquired immunodeficieney syndrome （AIDS）, a critical condition in humans in which progressive failure of the immune system allows life-threatening opportunis- tic infections. Over the past few years HIV has been spreading rapidly in the popula- tion. Almost, everyday there are thousands of new human cases of HIV infection being recorded in the world and these occur in almost every country of the world. However, the spread of HIV is relatively faster in the developing countries as compared to developed countries because developing countries have limited resources. Worldwide, 70% of HIV infections in the adults have been transmitted through heterosexual contact and vertical transmission accounts for more than 90~ of global infection in infants and children. In this paper, we propose a nonlinear mathematical model to study the spread of HIV by considering transmission of disease by heterosexual contact and vertical transmission. A stage structured model is proposed and analyzed by considering the total population variable and dividing the whole population under consideration into three stages： chil- dren, adults and old. Also, in this paper it is assumed that the rates of recruitment are different in different groups of population. Equilibria of the model and their stability are also discussed. Using the stability theory of differential equations and computer simu- lation, it is shown that due to the increase in the awareness of the disease in the adult class the total infective population decreases in the region under consideration.展开更多
基金This project has been funded in whole or in part with federal funds from the National Cancer Institute,National Institutes of Health, under contract N01-CO-12400
文摘More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.
文摘AIM： TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection （“anti-HBc alone”） among human immunodeficiency virus （HIV） type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS： Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus （HBV） infection were classified into three groups： past hepatitis, ＂anti-HBc alone＂ and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus （HCV） were performed on ＂anti-HBc alone＂ patients. RESULTS： One hundred and eighty seven （53.7%） HIV-positive patients had markers of HBV infection： 118 past infection （63.1%）, 14 chronic hepatitis （7.5%） and 55 ＂anti-HBc alone＂ （29.4%）. Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals （Cl） 1.33-4.00] and antibodies to HCV infection [odds ratio （OR） 2.87; 95% CI 1.10-7.48] were factors independently associated with the ＂anti-HBc alone＂ pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection （nor viral replication or HCV genotype）, or with HIV replication or CD4 level. No ＂anti-HBc alone＂ patient tested positive for HBV DNA. CONCLUSION： ＂Anti-HBc alone＂ prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,
文摘Clinical observations have demonstrated that excessive chronic alcohol use negatively affects human immuno- deficiency virus (HIV) infection and contributes to the liver manifestations of the disease, even in HIV mono- infection. HIV/hepatitis C virus (HCV) co-infection is as- sociated with increased progression of HVC liver disease compared to HCV infection alone, and both of these are negatively affected by alcohol use. Recent data suggest that alcohol use and HIV infection have common targets that contribute to progression of liver disease. Both HIV infection and chronic alcohol use are associated with increased gut permeability and elevated plasma levels of lipopolysaccharide; a central activator of inflammatory responses. Both alcoholic liver disease and HIV infec tionresult in non-specific activation of innate immunity, proinflammatory cytokine cascade upregulation, as well as impaired antigen presenting cell and dendritic cell functions. Finally, alcohol, HIV and antiretroviral therapyaffect hepatocyte functions, which contributes to liver damage. The common targets of alcohol and HIV infection in liver disease are discussed in this minireview.
文摘Squamous cell carcinoma of the anus （SCCA） is a com- mon cancer in the human immunodeficiency virus （HIV）- infected population, and its incidence continues to in- crease in male homosexuals. Combined chemoradiation with mitomycin C and 5-fiuorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy （HAART）, however, recent data indicate that： （1） most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and （2） this approach is associ- ated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recur- rence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in mid- dle-aged HIV-positive male homosexuals. In this popula- tion, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses （HPVs）. Large-scale cancer-prevention strategies （routine anuscopy and anal papanicolaou test- ing） should be implemented in this population. In addi- tion, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination.
文摘In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule： a residual level hepatitis B virus （HBV） DNA at 24 wk predicts beneficial outcome and reduced resistance at i year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.
基金This project was funded by the National Natural Science Foundation of China(No:397706830)
文摘Objective: Allelic polymorphisms of CCR5△32CCR2b-64I,CX3CR1-2491280M and SDF1-3'A associatedwith HIV-1 infection and disease progression wereinvestigated in indigenous Uygur populations from theXinjiang Uygur Autonomous Region of China. Methods: The study population comprised 316 healthyUygur subjects with an age range of 1-80 years old, fromwhom whole peripheral blood samples were collected andnone were HIV-1 seropositive. Genomic DNA samples werepurified using a Qiagen Blood Kit. Genotyping of theaforementioned four alleles was performed using PCR orPCR/RFLP assay, and further confirmed by direct DNAsequencing. Results: The allelic frequencies in Chinese Uygurpopulation were as follows: 3.48% for CCR5△32; 19.45% forCCR2b-64I; 13.8% for CX3CR1-2491280M haplotype, and20.41% for SDF1-3'A. Mutant allele distributions amongUygur populations were in accordance with theHardy-Weinberg equilibrium. No statistical difference wasfound between the frequency of the three HIV coreceptors andtheir respective ligand genes. Conclusion: The frequency of SDF1-3'A andCX3CR1-2491280M haplotypes in these Uygur populationswas similar to that of Caucasian people, while the frequency ofthe CCR2b-64I haplotype more closely matched the HanChinese. The frequency of CCR5△A32 in Uygur populationswas between Caucasian and Hall frequencies, the more closelymatching the frequency in Medi-Asia people. No geneticlinkage between any two of the three HIV coreceptor geneswas found, but obvious genetic linkages existed betweenCX3CR1-249I and CX3CR1-280M,with even higher linkagedegrees than Caucasian people.
基金Financially supported by Natural Science Foundation of China(No 39870725)Natural Science Foundation of Guangdong(No 980642)Research Foundation of Guangdong Education Bureau(No.20032).
文摘Objective: To analyze subtypes and quasi-species of isolatedviruses from HIV-1 infected individuals among the populationof Guangdong Province, for understanding the molecularepidemiological dynamics of local HIV-1 isolates, thus laying afoundation for designing a candidate AIDS vaccine. Methods: By hetero-duplex mobility assay (HMA) andsingle strand conformation poly-morphism (SSCP) analysison amplicons from single-primed polymerase chain reaction(SP-PCR), subtypes and quasi-species of tested HIV-1 isolateswere elucidated, and amplicons were sequenced forconfirmation. Results: Specific amplicons from different subtypes andquasi-species of HIV-1 could be discernible by HMA andSSCP analysis. Conclusion: HIV-1 isolates from different patients might beeither a different subtype or an identical subtype, and HIV-1isolates from an individual were present in a population ofquasi-species.
文摘Human immunodeficiency virus type 1 （HIV-1）, a causative agent of AIDS, is affecting today more than 35 millions of people worldwide. The advance of anti-HIV chemotherapy has made AIDS a chronic non-fatal disease in resourceful countries. Longawaited anti-HIV-1 vaccine is still not with us yet; however, great progress in structural analyses of the envelope protein of HIV-1 in recent years starts to shed light on rational intervention targeted at the envelope protein, as will be reviewed in this article.
文摘Human immunodeficiency virus （HIV） is a lenti-virus （a member of the retrovirus family） that causes acquired immunodeficieney syndrome （AIDS）, a critical condition in humans in which progressive failure of the immune system allows life-threatening opportunis- tic infections. Over the past few years HIV has been spreading rapidly in the popula- tion. Almost, everyday there are thousands of new human cases of HIV infection being recorded in the world and these occur in almost every country of the world. However, the spread of HIV is relatively faster in the developing countries as compared to developed countries because developing countries have limited resources. Worldwide, 70% of HIV infections in the adults have been transmitted through heterosexual contact and vertical transmission accounts for more than 90~ of global infection in infants and children. In this paper, we propose a nonlinear mathematical model to study the spread of HIV by considering transmission of disease by heterosexual contact and vertical transmission. A stage structured model is proposed and analyzed by considering the total population variable and dividing the whole population under consideration into three stages： chil- dren, adults and old. Also, in this paper it is assumed that the rates of recruitment are different in different groups of population. Equilibria of the model and their stability are also discussed. Using the stability theory of differential equations and computer simu- lation, it is shown that due to the increase in the awareness of the disease in the adult class the total infective population decreases in the region under consideration.
