Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and s...Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.展开更多
This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of re- combinant DNA （pCCMp24） and recombinant attenuated vaccinia virus Tian Tan （rddVTT_ccMpe4）. ...This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of re- combinant DNA （pCCMp24） and recombinant attenuated vaccinia virus Tian Tan （rddVTT_ccMpe4）. Intramuscular immuniza- tion was performed on days 0 （prime） and 21 （boost）. The immunogenicity of the vaccine schedules was determined by meas- uring human immunodeficiency virus （HIV）-specific binding antibody levels and cytokine （interleukin-2 and interleukin-4） concentrations in peripheral blood, analyzing lymphocyte proliferation capacity against HIV epitopes and CD4~/CD8＋cell ratio, and monitoring interferon-gamma levels at different times post-immunization. The results showed that pCCMp24, rddVTT.ccMp24 and their prime-boost immunization induced humoral and cellular immune responses. The pCCMp24/ rddVTT.ccMp24 immunization strategy increased CD8＋ T cells and induced more IFN-7-secreting cells compared with sin- gle-shot rDNA. The prime-boost immunization strategy also induced the generation of cellular immunological memory to HIV epitope peptides. These results demonstrated that prime-boost immunization with rDNA and rddVTT_ccMp24 had a tendency to induce greater cellular immune response than single-shot vaccinations, especially IFN-7 response, providing a basis for further studies.展开更多
目的了解经痘苗病毒天坛株(VTT)3次挑斑纯化筛选出的痘苗病毒减毒株广9株(VG9)的神经毒性和致病性。方法对痘苗病毒VG9和其亲代病毒VTT进行小鼠和乳鼠及家兔脑内毒力测定、裸鼠腹腔毒力测定及家兔皮内反应性实验,并观察实验动物的发病...目的了解经痘苗病毒天坛株(VTT)3次挑斑纯化筛选出的痘苗病毒减毒株广9株(VG9)的神经毒性和致病性。方法对痘苗病毒VG9和其亲代病毒VTT进行小鼠和乳鼠及家兔脑内毒力测定、裸鼠腹腔毒力测定及家兔皮内反应性实验,并观察实验动物的发病率和死亡率及皮肤坏死情况。结果两株病毒对小鼠和乳鼠的脑内毒力(icLD50)值显示,VTT株较VG9株分别强约100倍和18倍;对家兔脑内的毒力虽然icLD50值显示两株病毒相同,但VTT致家兔发病的数量较VG9多,其50%发病剂量较VG9多32倍。家兔皮内接种病毒后,较低病毒滴度(6.63 lg PFU)的VTT接种点出现严重的皮肤坏死,而VG9仅在较高滴度(7.54 lg PFU)接种点皮肤出现轻微坏死。结论通过不同途径接种几种实验动物均显示VG9的毒力较其母株VTT明显减弱。可以预测VG9痘苗在人体可能产生的不良反应较VTT痘苗低,并且有可能比VTT更适合作为痘苗病毒载体应用于新的重组疫苗(如HIV疫苗)的研发。展开更多
Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is rec...Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission.However,few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions,and their sensitivity to biocides.Here,we systematically measured the stability of vaccinia virus(VACV)under different environmental conditions and sensitivity to inactivation methods via plaque assay,quantitative real‐time polymerase chain reaction(qPCR),and Gaussia luciferase(G‐luciferase)reporter system.The results show that VACV is stable on the surface of stainless steel,glass,clothing,plastic,towel,A4 paper,and tissue and persists much longer at 4℃ and?20℃,but is effectively inactivated by ultraviolet(UV)irradiation,heat treatment,and chemical reagents.Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants,which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.展开更多
Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microen...Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.展开更多
Breast cancer,an unceasingly occurring neoplasm,is one of the major determinants of mortality in women.Several ineffective attempts have been pursued using with conventional therapies against breast cancer.Resistance ...Breast cancer,an unceasingly occurring neoplasm,is one of the major determinants of mortality in women.Several ineffective attempts have been pursued using with conventional therapies against breast cancer.Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses.Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells.Several different DNA-and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus,herpes virus,vaccinia,reovirus,Newcastle Disease virus,measles virus and vesicular stomatitis virus.This review aims to summarize the viro-therapeutical agents against breast malignancies.Key Scientific Concepts of Review:In this review paper,we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs.These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.展开更多
基金Supported by Dirección General de Asuntos del Personal Académico,Universidad Nacional Autónoma de México No.IN207514Consejo Nacional de Ciencia y Tecnología,Mexico,No.168098
文摘Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.
基金supported by the National Natural Science Foundation of China (81001342)the National Basic Research Program of China (2011CB512110)the National Mega Project on Major Infectious Diseases Prevention (2012ZX10001005-006)
文摘This study assessed and compared the immunogenicity of various immunization strategies in mice using combinations of re- combinant DNA （pCCMp24） and recombinant attenuated vaccinia virus Tian Tan （rddVTT_ccMpe4）. Intramuscular immuniza- tion was performed on days 0 （prime） and 21 （boost）. The immunogenicity of the vaccine schedules was determined by meas- uring human immunodeficiency virus （HIV）-specific binding antibody levels and cytokine （interleukin-2 and interleukin-4） concentrations in peripheral blood, analyzing lymphocyte proliferation capacity against HIV epitopes and CD4~/CD8＋cell ratio, and monitoring interferon-gamma levels at different times post-immunization. The results showed that pCCMp24, rddVTT.ccMp24 and their prime-boost immunization induced humoral and cellular immune responses. The pCCMp24/ rddVTT.ccMp24 immunization strategy increased CD8＋ T cells and induced more IFN-7-secreting cells compared with sin- gle-shot rDNA. The prime-boost immunization strategy also induced the generation of cellular immunological memory to HIV epitope peptides. These results demonstrated that prime-boost immunization with rDNA and rddVTT_ccMp24 had a tendency to induce greater cellular immune response than single-shot vaccinations, especially IFN-7 response, providing a basis for further studies.
文摘目的了解经痘苗病毒天坛株(VTT)3次挑斑纯化筛选出的痘苗病毒减毒株广9株(VG9)的神经毒性和致病性。方法对痘苗病毒VG9和其亲代病毒VTT进行小鼠和乳鼠及家兔脑内毒力测定、裸鼠腹腔毒力测定及家兔皮内反应性实验,并观察实验动物的发病率和死亡率及皮肤坏死情况。结果两株病毒对小鼠和乳鼠的脑内毒力(icLD50)值显示,VTT株较VG9株分别强约100倍和18倍;对家兔脑内的毒力虽然icLD50值显示两株病毒相同,但VTT致家兔发病的数量较VG9多,其50%发病剂量较VG9多32倍。家兔皮内接种病毒后,较低病毒滴度(6.63 lg PFU)的VTT接种点出现严重的皮肤坏死,而VG9仅在较高滴度(7.54 lg PFU)接种点皮肤出现轻微坏死。结论通过不同途径接种几种实验动物均显示VG9的毒力较其母株VTT明显减弱。可以预测VG9痘苗在人体可能产生的不良反应较VTT痘苗低,并且有可能比VTT更适合作为痘苗病毒载体应用于新的重组疫苗(如HIV疫苗)的研发。
基金supported by funds from the National Key R&D Program of China (2022YFE0203100)the CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-038 and CIFMS 2022-I2M-1-021)the National Natural Science Foundation of China (82271802,82241075,and 82072288).
文摘Monkeypox(mpox)outbreak in 2022 has caused more than 91,000 cases,has spread to 115 countries,regions,and territories,and has thus attracted much attention.The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission.However,few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions,and their sensitivity to biocides.Here,we systematically measured the stability of vaccinia virus(VACV)under different environmental conditions and sensitivity to inactivation methods via plaque assay,quantitative real‐time polymerase chain reaction(qPCR),and Gaussia luciferase(G‐luciferase)reporter system.The results show that VACV is stable on the surface of stainless steel,glass,clothing,plastic,towel,A4 paper,and tissue and persists much longer at 4℃ and?20℃,but is effectively inactivated by ultraviolet(UV)irradiation,heat treatment,and chemical reagents.Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants,which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.
基金supported by the National Natural Science Foundation of China(Grant No.81830006)the Science Technology Department of Zhejiang Province(Grant No.2021C03117).
文摘Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.
文摘Breast cancer,an unceasingly occurring neoplasm,is one of the major determinants of mortality in women.Several ineffective attempts have been pursued using with conventional therapies against breast cancer.Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses.Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells.Several different DNA-and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus,herpes virus,vaccinia,reovirus,Newcastle Disease virus,measles virus and vesicular stomatitis virus.This review aims to summarize the viro-therapeutical agents against breast malignancies.Key Scientific Concepts of Review:In this review paper,we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs.These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.
