Lymphadenopathy in connection with human herpes virus type 6 (HHV-6) infection

Summary Two siblings and their mother developed afebrile generalized lymphadenopathy. The lymph nodes were movable and painless. During the course of the illness, the mother and one child developed an uncharacteristic rash. Increased titers of human herpes virus type 6 (HHV-6) antibodies were found in all three family members and in an unrelated patient with lymphadenitis colli. The enlarged lymph nodes decreased in size within several weeks. We speculate these symptoms to be caused by an infection with this lymphotropic virus.     

Acyclovir resistant genital herpes virus infection in a patient with AIDS.

Three acyclovir resistant strains of HSV-2 were isolated from mucoulcerative lesions in a patient suffering from AIDS in whom the oral and intravenous acyclovir treatment was unsuccessful. All the isolates were classified by monoclonal antibodies and showed no differences in DNA restriction patterns.     

Detection of antibody to viral proteins following primary infection with herpes simplex virus

Sera from patients with primary genital infection with herpes simplex virus (HSV) were tested by immunoblotting (IB) and radioimmunoprecipitation (RIP) analysis to determine the protein targets of antibody elicited by infection. The two tests detected antibody to different antigens: IB primarily detected reactivity with p40, a phosphorylated capsid protein, and RIP detected antibody to glycoprotein B, a viral envelope component. Furthermore, RIP detected antibody at an earlier stage of infection then IB. A nondenaturing version of IB was developed and used to investigate the role that the solubilisation of antigen plays in the sensitivity of each test for antibodies with different specificities.     

Immunohistochemical detection of the human herpes virus 8 (HHV8) latent nuclear antigen-1 in Kaposi's sarcoma

AIMS: The molecular genetics of the human herpes virus 8 (HHV8) has now been characterised and the virus appears to be important in the pathogenesis of Kaposi's sarcoma (KS). This study attempts to determine the rate of HHV8 infection in KS in an Australian cohort. METHODS: Routine streptavidin-biotin-peroxidase immunostaining with diaminobenzidine was performed on paraffin-embedded archival tissues of 37 KS cases using a murine monoclonal antibody directed against the C-terminus of the latent nuclear antigen-1 molecule of HHV8 (clone 13B10; Novocastra) at 1:50 dilution. RESULTS: Positive HHV8 nuclear staining was detected in the nuclei of the spindle cells and endothelial cells of the vascular channels in about 78% (29/37) of all cases. HHV8 staining was absent in the non-neoplastic vessels in the adjacent tissue (P=0.0001, chi(2)=44.46; chi(2)-test with continuity correction) and the negative control cases of Merkel cell carcinoma (P=0.02, chi(2)=5.07; chi(2)-test with continuity correction). HHV8 staining was detected in 80% (8/10 cases) of the patch stage, 88% (7/8 cases) of the plaque stage and 74% (14/19 cases) of the late stage. No significant difference was found between HHV8 positivity and HIV status, age, gender, tumour recurrence, multiplicity or site of the lesions. CONCLUSIONS: The latent nuclear antigen-1 of HHV8 can be detected by immunohistochemistry in the majority of human KS lesions, raising the possibility of its future potential use as an adjunct for the diagnosis of KS in problematic cases.     

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.     

Atypical presentation of herpes simplex (chronic hypertrophic herpes) in a patient with HIV infection

A 46-year-old man with HIV infection and AIDS presented with a large perianal ulcerated vegetative lesion that developed over a 1-year period. He had a past history of recurrent genital herpes infection, treated successfully each time with acyclovir. The perianal lesion developed while he was taking prophylactic acyclovir. Clinically, there were features suspicious of a carcinoma and a biopsy was reported as showing dysplasia. Therefore, the lesion was resected in its entirety. Histologically, there were prominent pseudo-epitheliomatous hyperplasia and chronic ulceration associated with herpesvirus infection. There was no evidence of dysplasia or malignancy. It is important to be aware of chronic vegetant herpesvirus infection, as clinical appearances are unusual and some methods of identification, such as smears or biopsy, may not be sufficient for diagnosis. Viral culture or PCR may need to be performed for a definite diagnosis to alleviate prolonged discomfort and avoid unnecessary radical surgery.     

人疱疹病毒6型感染与神经胶质瘤关系的初步研究

目的探讨人疱疹病毒6型（human herpesvirus-6,HHV-6）感染与神经胶质瘤的关系。方法将辽宁省肿瘤医院神经外科2011年6月-2013年5月收治的神经胶质瘤患者45例纳入病例组,将同期该医院收治且已排除神经胶质瘤的脑外伤患者45例作为对照组。分别采用巢式聚合酶链式反应（nested polymerase chain reaction,Nested—PCR）法检测两组研究对象人病变脑组织样本中HHV-6序列;采用免疫组化染色法检测两组研究对象人病变脑组织样本中HHV-6抗原的表达。结果病例组HHV石DNA阳性率为31．11％,对照组HHV-6DNA阳性率为6．67％（χ2=8．755,P=0．003）。病例组HHV-6早期抗原041表达阳性率为22．22％,对照组HHV-6早期抗原p41表达阳性率为0．00％（χ2=11．250,P=0．001）。病例组HHV-6DNA阳性率、HHV-6抗原阳性率均高于对照组,组间差异有统计学意义（P〈0．05）。结论神经胶质瘤患者和非神经胶质瘤脑外伤患者病变脑组织中HHV石感染率有差异,据此推断HHV-6感染在神经胶质瘤的发生和发展过程中起到一定的作用。     

Experimental infection of human leukocytes with parainfluenza 1 (6/94) virus.

Parainfluenza 1 (6/94) virus replicated in both unstimulated and phytohemagglutinin (PHA)-stimulated human peripheral blood leukocytes (PBL). After exposure of PBL to 6/94 virus at a multiplicity of infection of 1, the presence of viral antigen was demonstrated by immunofluorescence in the cytoplasm of less than 1% of unstimulated PBL and 1 to 5% of macrophages. Small amounts (less than 50 mean egg infective doses per ml in most instances) of cell-free virus were present in 18 of 30 (60%) cell cultures tested from 3 to 8 days postinfection. Cell-free virus peaked 6 days postinfection. Virus replication was enhanced in PHA-stimulated cells. Approximately 1 to 10% of PHA-stimulated PBL contained viral antigen as evidenced by immunofluorescence, and cell-free virus was present in 19 of 25 (76%) of the cell cultures tested from 3 to 8 days postinfection. Paramyxovirus nucleocapsids and tubular aggregates were seen in the cytoplasm of approximately 5% of PHA-stimulated PBL and were visualized only in lymphocytes. No other unusual intracytoplasmic or intranuclear structures were seen.     

Neutralising antibody in mice with primary and recurrent herpes simplex virus infection

Summary Neutralising antibody was studied in mice infected in the ear with herpes simplex virus type 1. Antibody was detected six days after infection and after one month it had reached titres which subsequently varied little. Geometric group mean titres were doubled by reinoculation of virus whereas recurrent disease induced by trauma did not change them (although titres did change in some individual animals).Mean titres in mice which had had unequivocal signs of primary disease were twice as high as in those which had not, and the frequency of recurrent disease in response to trauma in the former animals was greater than in the latter. A reduction in the frequency of induced recurrent disease was seen if the application of trauma was delayed for some time after the establishment of latency.Hyperimmunisation increased mean titres tenfold. If given soon after primary infection it reduced the frequency of induced recurrent disease but if its administration was delayed then the frequency was increased.     

Human herpes virus type 6 (HHV-6) and its in vitro effect on human immunodeficiency virus (HIV).

Human herpes virus type 6 (HHV-6) was isolated from the peripheral blood lymphocytes of a patient infected with human immunodeficiency virus (HIV). Antibodies to this herpes virus were found to be widespread among adults and children in Western Australia. Co-infection studies indicated that HIV replication was inhibited by the presence of HHV-6.     

Epidemiology of human herpes virus 8 (HHV-8) or the herpes virus associated with Kaposi's sarcoma (KSHV)

Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma-associated herpesvirus (KSHV), is not a ubiquitous virus. In countries with a low viral seroprevalence (< 5% in adult general population) as the USA, Northern Europe and Asia, the infection concerns essentially homosexual men. In this latter population, the viral transmission seems to occur during sex. In endemic countries (HHV-8 seroprevalence between 10-70% in the adult general population) as in the Mediterranean basin (Italy, Greece), and Africa (East and Central Africa), men, women and children are infected. In these countries, HHV-8 seroprevalence increases with age and often reaches adult rates before the end of puberty. Viral transmission, in general endemic populations, seems to occur from mother to child and between sibs whereas heterosexual transmission appears to concern essentially groups at risk for sexual transmitted diseases. Saliva is a major reservoir of HHV-8.     

Detection of human herpes virus type 6 DNA in precancerous lesions of the uterine cervix

Human herpes virus type 6 (HHV-6) DNA has been suggested to be a cofactor to human papillomavirus (HPV) in cervical cancer. In a cross-sectional study, we investigated the association between HHV-6 DNA detected in cervical brushings and high-grade squamous intraepithelial lesions (HSIL), while controlling for genital infection with 27 genotypes of HPV. Of the 320 women recruited from an oncologic gynecology clinic, 50 had invasive cervical cancer, 65 had HSIL, 80 had low-grade squamous intraepithelial lesions (LSIL), and 125 were normal. Four of the seven HHV-6-positive women had HSIL. HHV-6 was associated with HSIL after adjusting for age and socioeconomic status (odds ratio [OR] of 10.9, 95% confidence interval [CI]: 1.1-107.1). This association was no longer significant after controlling for HPV (OR = 6.4, 95% CI = 0.3-128.5). HHV-6 was detected in cervical samples from women with precancerous and cancerous lesions of the cervix, but not significantly more frequently than in normal women.     

Centrifugal enhancement of human immunodeficiency virus (HIV) and human herpesvirus type 6 (HHV-6) infection in vitro

The effect of centrifugal inoculation of human immunodeficiency virus (HIV) and human herpesvirus-6 (HHV-6) on the infectivity of the viruses for cell cultures was examined. Three HIV-1 strains, ARV-2, HTLV-IIIb and a local isolate, WA-46c, were tested in peripheral blood lymphocytes, HUT-78, H9 and MT-2 cells. The HHV-6 strain was a local isolate and was studied only in peripheral blood lymphocyte cultures. Centrifugal inoculation of the viruses at a force of 2500 x g for 60 min, enhanced HIV-1 infectivity by a factor of about 10-fold in all cell cultures tested. Infectivity was increased about 100-fold for HHV-6.     

Cell-mediated cytotoxic responses in lungs following a primary bovine herpes virus type 1 infection.

Non-major histocompatibility complex (MHC) restricted cytotoxicity is an important part of the immune reaction mounted in response to bovine herpes virus type 1 (BHV-1) infection. In this study, we evaluated the effect of BHV-1 infection on the ability of lung parenchyma leucocytes (LPL), cranial tracheobronchial lymph node cells (BLNC) and peripheral blood mononuclear leucocytes (PBML) to mediate this function. While LPL from non-infected calves mediated cytotoxicity against BHV-1-infected cells, a similar activity could not be detected in PBML or BLNC. In contrast, both LPL and PBML from naive calves could mediate cytotoxicity against K562 target cells but only after activation with interleukin-2 (IL-2). BLNC were unable to kill K562 cells. Infection of calves with BHV-1 enhanced the ability of LPL and PBML to kill BHV-1-infected cells. This enhancement was detected as early as Day 1 after infection in LPL whereas it could only be detected in PBML 8 days after infection. The results demonstrate that the leucocyte population present at the site of infection was able to mediate a potentially important antiviral function and that this function was enhanced rapidly in response to infection. Thus LPL-mediated cytotoxicity may be an important mechanism for the recovery from BHV-1 infection.     

Persistent infection of human lymphoid and myeloid cell lines with herpes simplex virus.

Herpes simplex virus (HSV) type 1 replicated and persisted in human T, B, and myeloid cell lines with different patterns of viral replication and various effects on cell growth. T cell line CEM supported the replication of HSV for over 400 days without detectable differences in cell growth as compared with uninfected cells. HSV persisted in B cell line NC37 and myeloid cell line K562 for up to 222 and 374 days, respectively, but led to a significant decrease in the number of viable cells by 7 weeks of infection. The average number of cells producing infectious virus was very low in these cell lines (range, 0.5 to 2.7+) compared with a larger proportion of cells exhibiting HSV antigens by immunofluorescence (range, 24 to 58%). In contrast, null cell line LAZ 221 failed to replicate HSV even though the viral infection led to a cessation of cell growth.     

Isotype immune response of IgG antibodies at the persistence and reactivation stages of human herpes virus 6 infection.

BACKGROUND: Infections with human herpes virus 6 (HHV-6) are very common. After primary infection, the virus remains latent and persists at low level in cells and tissues. Not usually associated with disease in the immunocompetent host, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed. The different stages of HHV-6 infection are difficult to characterize in the laboratory. OBJECTIVES: The aim of this paper was to assess the isotype patterns of IgG antibodies against HHV-6 in seropositive subjects during different stages of the virus activity. STUDY DESIGN: From a total of 190 human serum samples from 43 healthy children, 24 pregnant women and 24 patients with bone marrow transplants, 111 sera were processed by indirect immunofluorescence assay for the detection of IgG1, IgG2, IgG3 and IgG4 specific antibodies. The mean geometrical title (MGT) of the antibodies was calculated. RESULTS: All pregnant women had IgG1 (24/24; 100%; MGT 46). A 95% (41/43) of healthy infants had IgG1 (MGT 57). In bone marrow transplants, 58% (14/24) of the patients showed seroconversion (MGT 529) with an isotype response of IgG1 and IgG4 during the observation period. Remaining bone marrow transplant patients, who had the IgG without any variations (MGT 184), had isotype IgG1. CONCLUSIONS: These results revealed two different immune isotype response patterns. One of them is restrictive to IgG1 in the latent phase of HHV-6 infection in healthy children, pregnant women and transplant patients with stable levels of antibodies whereas IgG1 and IgG4 are detected in the reactivation of HHV-6 in transplant patients. The IgG isotype immune responses may contribute to the existing set of serological markers in characterizing the different stages of natural infection of HHV-6.