人乳头瘤病毒感染与人乳头瘤病毒疫苗的研究进展

人乳头瘤病毒(HPV)感染与宫颈癌的发生密切相关,是宫颈癌发生的最主要诱发因素.预防性HPV疫苗是一种预防宫颈癌的新方法,其效果得到了多项临床试验的肯定.治疗性HPV疫苗的研发同样备受关注,目前治疗性疫苗的类型很多,但因其机制较复杂,大多仍处在实验阶段.     

Simian virus 40 infection in humans and association with human diseases: results and hypotheses

Simian virus 40 (SV40) is a monkey virus that was introduced in the human population by contaminated poliovaccines, produced in SV40-infected monkey cells, between 1955 and 1963. Epidemiological evidence now suggests that SV40 may be contagiously transmitted in humans by horizontal infection, independent of the earlier administration of SV40-contaminated poliovaccines. This evidence includes detection of SV40 DNA sequences in human tissues and of SV40 antibodies in human sera, as well as rescue of infectious SV40 from a human tumor. Detection of SV40 DNA sequences in blood and sperm and of SV40 virions in sewage points to the hematic, sexual, and orofecal routes as means of virus transmission in humans. The site of latent infection in humans is not known, but the presence of SV40 in urine suggests the kidney as a possible site of latency, as it occurs in the natural monkey host. SV40 in humans is associated with inflammatory kidney diseases and with specific tumor types: mesothelioma, lymphoma, brain, and bone. These human tumors correspond to the neoplasms that are induced by SV40 experimental inoculation in rodents and by generation of transgenic mice with the SV40 early region gene directed by its own early promoter-enhancer. The mechanisms of SV40 tumorigenesis in humans are related to the properties of the two viral oncoproteins, the large T antigen (Tag) and the small t antigen (tag). Tag acts mainly by blocking the functions of p53 and RB tumor suppressor proteins, as well as by inducing chromosomal aberrations in the host cell. These chromosome alterations may hit genes important in oncogenesis and generate genetic instability in tumor cells. The clastogenic activity of Tag, which fixes the chromosome damage in the infected cells, may explain the low viral load in SV40-positive human tumors and the observation that Tag is expressed only in a fraction of tumor cells. "Hit and run" seems the most plausible mechanism to support this situation. The small tag, like large Tag, displays several functions, but its principal role in transformation is to bind the protein phosphatase PP2A. This leads to constitutive activation of the Wnt pathway, resulting in continuous cell proliferation. The possibility that SV40 is implicated as a cofactor in the etiology of some human tumors has stimulated the preparation of a vaccine against the large Tag. Such a vaccine may represent in the future a useful immunoprophylactic and immunotherapeutic intervention against human tumors associated with SV40.     

A persistent infection of baby hamster kidney-21 cells with mumps virus and the role of temperature-sensitive variants.

A persistent infection of baby hamster kidney-21 (BHK-21) cells with mumps virus (BHKpi) was maintained for over 60 cell passages in the absence of antiserum. Viral persistence was demonstrated in the cultures by hemadsorption, immunofluorescence, multinucleate syncytia, and released mumps virus at the level of 10(2)--10(3) fluorescent focus-forming units/ml. No detectable levels of interferon were found in cultures persistently infected with mumps virus. Approximately 85--95% of the cells contained viral antigens. Nuclear fluorescence was observed in the persistently infected cells. Mumps virus from persistently infected clutures (MuVpi) was more heat-labile than wild-type mumps (MuVo) when subjected to 40 degrees C. BHKpi cells had a more rapid doubling time and a higher cloning efficiency in soft agar in comparison to BHK-21 cells. MuVpi was also found to be temperature-sensitive. The temperature-sensitivity of MuVpi was determined by the efficiency of plating at 33 degrees and 39 degrees C. MuVpi readily established a persistent infection in BHK-21 cells with less cytopathology than MuVo, and released temperature-sensitive virus.     

The role of an immunoperoxidase technique in the diagnosis of oral herpes simplex virus infection in patients with leukemia

Laboratory techniques are often used to confirm a clinical diagnosis of oral herpes simplex virus (HSV) infection in patients with leukemia. In the present study, an immunoperoxidase technique (IPT) was used to examine smears taken from the oral mucosa of 44 patients with leukemia at Vancouver General Hospital. It was found that the IPT was as sensitive and specific as viral culture in confirming the presence of HSV. The IPT was found to be more predictive of symptomatic oral HSV disease than viral culture because it did not give positive results if there was only viral shedding in the absence of clinical disease. As the IPT is rapid and inexpensive as well as being specific, sensitive, and predictive, it has a definite role in the laboratory confirmation of oral HSV lesions in leukemics.     

Hepatitis E virus infection in Latin America: A review

Data reported during recent years reveal the complex picture of the epidemiology of hepatitis E virus (HEV) infection in Latin America. Whereas in countries like Argentina and Brazil is almost identical to the characteristic of most countries from North America and Europe, HEV in the Caribbean and Mexico involves the water‐borne, non‐zoonotic viral genotypes responsible for epidemics in Asia and Africa. Nevertheless, Latin America has been considered a highly endemic region for hepatitis E in the scientific literature, a generalization that ignores the above complexity. In addition, reports from isolated Amerindian communities, which display well known, important and very specific epidemiological features for hepatitis B and D virus infections are neither taken into account when considering the epidemiology of hepatitis E in the region. This review updates compilation of the available information for the HEV infection, both among humans and other mammals, in Latin America, discusses the strengths and the weaknesses of our current knowledge, and identifies future areas of research. J. Med. Virol. 85: 1037–1045, 2013. © 2013 Wiley Periodicals, Inc.     

Lack of complement-dependent cytolytic antibodies in hepatitis A virus infection

Sera collected from patients with acute hepatitis A virus (HAV) infection and convalescent sera were examined for cytolytic activity against HAV-infected human-embryo lung fibroblasts (HAV carrier fibroblasts). Using the 51chromium release assay, no complement dependent antibody mediated cytolytic activity against HAV carrier cells could be detected. In control experiments with identical cell strains, anti-herpes simplex virus (HSV) positive sera and complement caused specific lysis of HSV type 1 infected target cells. The data presented here do not support the hypothesis that in the possible immunopathogenesis of HAV infection, complement-dependent cytolytic antibodies play an essential role.     

The role of respiratory virus infection in suspected pertussis: A prospective study

BackgroundInfections caused by Bordetella pertussis are frequent and responsible for cases of huge severity in unvaccinated young infants. However, clinical manifestations vary and mimic other respiratory diseases as respiratory viruses.MethodsA prospective cohort study was performed with infants under 1 old, hospitalized with suspected pertussis. All infants were submitted to etiological research to identify Bordetella pertussis (nasopharynx swab for culture and/or PCR) and respiratory viruses (nasopharyngeal aspirate for indirect immunofluorescence). Clinical and demographic data were collected.ResultsAmong 59 infants, an etiological agent was identified in 37 (62.8%). Respiratory virus was identified in 19 (32%) and Bordetella pertussis in 14 (23.7%) as sole agent. Codetection was found in 4 (7%). Younger age, absence of fever, lack of BP immunization, leukocytosis > 20,000/mm³, lymphocytosis >10,000/mm³ were associated to a greater chance of pertussis. Wheezing and living with siblings were associated with viral infection. After adjustment for confounders, the most important predictors were presence of wheezing for respiratory virus and leukocytosis for pertussis. The severity of infections by RV and BP were similar.ConclusionRespiratory virus infections are frequent in cases of clinical suspicion of pertussis and may actually exceed the prevalence of BP. Clinical/laboratory characteristics may suggest the etiology, but they are not pathognomonic, which stresses the need for respiratory virus and Bordetella pertussis research in this clinical situation.     

Concurrent hepatitis C virus and hepatitis delta virus superinfection in patients with chronic hepatitis B virus infection.

Since hepatitis C virus (HCV) and hepatitis delta virus (HDV) are transmitted by the same routes as hepatitis B virus (HBV), simultaneous or concurrent HCV and HDV infection in patients with chronic HBV infection may occur. To test this hypothesis and to examine the clinicohistological and immunopathological presentations of such multiple hepatitis virus infections, acute and/or convalescent serum specimens from 86 patients with acute HDV superinfection were tested by enzyme immunoassay for antibodies to HCV. Of the 86 patients, 18 (20.9%) were associated with HCV infection. Although patients with early mortality cannot be evaluated by the HCV markers used in this study, the results showed that the clinical and histologic features were similar except that patients with HCV infection were older than those without HCV infection (P less than 0.01). Immunopathological studies carried out within 2 months after the onset of acute HDV superinfection demonstrated that hepatitis B core antigen (HBcAg) was not detected in any patient and HDV antigen was detected in 18.2% of the patients with HCV infection whereas HBcAg and HDAg were found in 7% and 65.1%, respectively, of those without HCV coinfection (P less than 0.02). It is concluded that concurrent HCV and HDV superinfections can and do occur in patients with chronic HBV infection. In these triple viral infections, HCV may even transiently suppress HDV and HBV.     

The role of infection and inflammation in sudden infant death syndrome

Sudden Infant Death Syndrome (SIDS) is the most common cause of post-neonatal mortality in the developed world. The exact cause of SIDS is likely to be multifactorial involving a critical developmental period, a vulnerable infant, and one or more triggers. Many SIDS infants have a history of viral illness preceding death. Prone sleep position, one of the leading risk factors, can increase airway temperature, as well as stimulate bacterial colonization and bacterial toxin production. Markers of infection and inflammation are often found on autopsy along with microbial isolates. Although the causal link between infection and SIDS is not conclusive, there is evidence that an infectious insult could be a likely trigger of SIDS in some infants.     

Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis

ObjectivesTo provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic Gen-Probe Prodesse assays—on the detection of viral respiratory infections.MethodsA comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay.ResultsTwenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848–0.949), 0.949 (95% confidence interval, 0.882–0.979) and 0.954 (95% confidence interval, 0.871–0.985), respectively. The three mPCRs were comparable in terms of detection of FluA.ConclusionsPoint estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.     

A critical role of IL-17 in modulating the B-cell response during H5N1 influenza virus infection

Interleukin-17 (IL-17), a member of the IL-17 cytokine family, plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung. Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections, little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection. In this study, we show that H5N1-infected IL-17 knockout (KO) mice exhibit markedly increased weight loss, more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls. Moreover, the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection, which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice. Consistent with this observation, B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture. Taken together, these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.     

Generalized herpes simplex virus infection in an immunocompromised patient--report of a case and review of the literature

Patients with immunodeficiency or treatment-related immunosuppression are at an increased risk of developing severe herpes simplex virus (HSV) infection. We present a fatal case of a generalized HSV-1 infection in a 22-year-old female afflicted by acute lymphoblastic leukemia who was treated with polychemotherapy. The terminal clinical course was characterized by abdominal pain, progressive hepatic failure, and disseminated intravascular coagulation. Autopsy revealed non-perioral herpetic skin lesions and mucosal ulceration of the esophagus and colon. Punctuated areas of yellow-tan necrosis with hyperemic rims were detected in the liver, spleen, and lung. Numerous petechiae were observed on the mucosal surface of the esophagus, jejunum, ileum, and colon. Microscopically, lesions demonstrated the cellular changes characteristic of herpetic infection. Immunohistochemistry for identification of the virus using monoclonal antibodies against HSV-1 and HSV-2 showed positive staining for HSV-1. Polymerase chain reaction and sequencing confirmed HSV-1 positivity. Emphasis must be placed on clinical awareness of a generalized HSV infection in immunocompromised patients. Absence of orofacial or genital lesions does not rule out the possibility of active HSV infection.     

Thrombophlebitis and upper respiratory tract virus infection

During an episode of thrombophlebitis, the 72-year-old correspondent came down with a common cold presumably, but not provenly, due to infection by one of the rhinoviruses. During the 96 hr period of coryza, all symptoms of thrombophlebitis vanished completely. There is experimental evidence that rhinovirus infections elicit cytokine production [St?ckl et al. (1999): J Clin Invest 104: 957-965], and that IL-10 can assuage thrombosis in rats [Downing et al. (1998): J Immunol 161: 1471-1476].     

EB病毒与人疱疹病毒6型感染在药疹发生中的作用

目的 本研究主要就人疱疹病毒6型(HHV-6)与EB病毒(EBV)感染在药疹产生过程中的作用展开分析,以此来为药疹患者的临床治疗提供参考.方法 选择我院2012年12月--2013年12月所收治的62例药疹患者作为观察组,另选148例健康献血人员作为对照组,采用巢式PCR对HHV6 DNA进行检测、采用PCR-Southern对EBV DNA进行检测、采用ELISA法对EBV VCA-IgM进行检测,并对其检测结果进行比较.结果 两组患者的EBV DNA、HHV6 DNA、EBV VCA-IgM阳性率存在明显差异,具有统计学意义(P＜0.05).结论 绝大部分药疹患者存在EBV感染的情况,且EBV感染与HHV6感染之间存在相互激活的作用,在药疹诊断过程中具有较高的临床应用价值,可以将其作为药疹的临床诊断指标之一.     

Haemolysis in hepatitis A virus infections coinciding with the occurrence of autoantibodies against triosephosphate isomerase and the reactivation of latent persistent Epstein-Barr virus infection

Haemolysis has been observed frequently as a complication of acute hepatitis A virus (HAV) infection. However, the pathogenic mechanism has not been elucidated completely. In individual cases the detection of anti-erythrocyte antibodies of unknown specificity was described. The raised serum IgM fraction was shown to consist partially of autoantibodies. Previously, we detected autoantibodies of immunoglobulin class M directed against triosephosphate isomerase (IgM anti-TPI) in patients with infectious mononucleosis. These autoantibodies are able to induce haemolysis. In this study the occurrence of IgM anti-TPI in acute HAV infections and other viral diseases has been investigated. In 33 of 134 patients suffering from HAV infection (IgM anti-TPI was detected. Haematological and chemical data were available from seven of these 33 patients. Mild-to-moderate signs of haemolysis correlating with the IgM anti-TPI titre in the follow-up examinations were demonstrated. The presence of IgM anti-TPI in HAV infections is connected with a reactivation of a latent persistent EBV infection. In other viral infections both the detection of IgM anti-TPI and evidence of a reactivated EBV infection is rare. Thus, we anticipate that IgM anti-TPI antibodies occurring with the reactivation of a latent persistent EBV infection take part in provoking haemolysis in acute HAV infections. © 1996 Wiley-Liss, Inc.     

Women's willingness to be tested for human immunodeficiency virus during pregnancy: A review

Mother-to-child-transmission of human immunodeficiency virus(HIV) is a primary cause of pediatric infections with HIV. Many of these infections involve women who were not tested early enough in pregnancy, or who didnot receive prevention services. HIV testing of pregnant women is considered to be one of the key strategies for preventing mother-to-child-transmission of HIV, but HIV testing rates among pregnant women in various countries remain suboptimal. Understanding the factors relating to women's willingness to be tested for HIV during pregnancy is critical for developing strategies to increase HIV testing rates among pregnant women. Extensive research points to various factors relating to women's willingness to be tested for HIV during pregnancy, and various recommendations aimed at improving testing rates among pregnant women have been suggested based on the research. In light of the goals set by the United Nations to reduce the rate of infants infected with HIV, it is necessary to summarize what is currently known regarding factors related to women's willingness to be tested for HIV during pregnancy. The purpose of this review is therefore to examine factors related to women's willingness to be tested for HIV during pregnancy, and to summarize recommendations for practice and further research.     

Histopathological changes in simian immunodeficiency virus infection

The histological lesions were studied in seven rhesus and three cynomolgus monkeys infected with simian immunodeficiency virus for periods ranging from nine weeks to 18 months. Lymphoreticular changes included hyperplasia, follicular involution and depletion, and one animal had amyloidosis of the spleen. Hyperplastic changes also took place in mucosa-associated lymphoid tissue and infiltrations occurred in the vaginal mucosa of one animal, which could be significant in sexual transmission of the infection. The range of opportunistic infections was small compared with that in human AIDS patients, although two monkeys had Pneumocystis carinii pneumonia. Enterocolitis was a common finding and brown adipose tissue was transformed into a large vacuolated type. Lesions of the central nervous system were found in five of nine monkeys, and consisted of foci of glial activity and perivascular and meningeal lymphocytic infiltration. A lymphoma involving the lumbar spinal cord developed in one animal.