Sylvia D. Gardner

The JC virus antibody response in serum and cerebrospinal fluid in progressive multifocal leucoencephalopathy

BACKGROUND A clinical diagnosis of progressive multifocal leucoencephalopathy (PML) can be confirmed by histological or virological examination of brain material. Whilst a less invasive method is provided by the detection of JC DNA in cerebrospinal fluid (CSF), very few studies have been done to assess the value of JC virus (JCV) serology in PML diagnosis. OBJECTIVES To study the JCV antibody response in the serum and CSF of PML patients. STUDY DESIGN A retrospective study was done using haemagglutination inhibition (HI), M-antibody capture radioimmunoassay (MACRIA) and JC-specific oligoclonal IgG banding on one or more sera and/or CSFs from 28 confirmed PML patients. Seventy-one serum and CSF samples were tested from patients with memory loss or dementia as a control group. RESULTS Twenty-seven PML patients (96%) had detectable JCV HI antibody in the serum, with titres ranging from 1 : 10 to > 1 : 20480, compared to 48 (68%) of the controls (P = <0.005). JCV IgM antibody was detected in the serum of 12/22 (55%) PML patients. JCV HI antibody was detected in the CSF in 12 of 18 (67%) PML patients, antibody index measurements being used to control for a possible breakdown of the blood-brain barrier. Intrathecal JCV antibody was not found in any control patient. Locally produced JCV-specific IgG bands were detected in the CSF of 7 PML patients tested, confirming the intrathecal origin and specificity of the HI antibody. CONCLUSIONS The presence of intrathecal JCV antibody indicates active central nervous system infection with JC virus, and provides a useful diagnostic test for PML, with a sensitivity of 67% and a specificity of 100%. The absence of serum JCV antibody nearly always excludes a diagnosis of PML, but the titre of antibody, IgG or IgM, correlates with the underlying condition rather than the development of neurological symptoms.

The isolation of parainfluenza 4 subtypes A and B in England and serological studies of their prevalence

The term parainfluenza viruses was proposed for certain members of the myxovirus group which resembled the influenza viruses but which were not related to them antigenically (Andrewes, Bang, Chanock & Zhdanov, 1959). Included in this group were parainfluenza virus types 1, 2 and 3. Parainfluenza 2 (Croup associated or CA virus) was first described by Chanock in 1956, and parainfluenza 1 and 3 (Haemadsorption types 2 and 1 or HA-2 and HA-1) by Chanock and his colleagues in 1958. In 1960 Johnson, Chanock, Cook & Huebner described a new haemadsorption virus which they called M-25. This strain was isolated from a college student and also from 30 infants in an orphanage nursery and was shown to be antigenically distinct from parainfluenza 1, 2 and 3 viruses. They proposed that M-25 should be the prototype strain for parainfluenza type 4. In 1964 Canchola and his colleagues described a new strain which could not be identified with an antiserum prepared against the prototype parainfluenza type 4 (M-25) virus. They had isolated 25 strains but only two of these resembled M-25. The remaining 23 strains had a common complement fixing antigen but could be differentiated in neutralization tests. The two groups of strains were called parainfluenza 4 subtypes A and B respectively. For the first time also these workers were able to report an association of type 4 virus with respiratory disease in children. In 1966 Zilisteanu and his colleagues reported the isolation of eight further strains of parainfluenza 4 subtype A. These were obtained from children in a nursery in Bucharest. Following an outbreak of measles, 12 of the children had mild respiratory signs, nasal obstruction, nasal catarrh, tracheitis and pharyngitis, but were afebrile and well, apart from these manifestations. From these reports it appears that isolation of parainfluenza 4 virus is difficult because of the slow growth in cell culture and weak haemadsorption pattern and that infection with these strains produces a very mild respiratory illness mainly in young children. Since 1962 in this laboratory all haemadsorbing viruses which could not be immediately identified have been stored at — 70° C. For the most part these strains came from other laboratories situated in different parts of the country. This report is based on: (1) the identification of 18 strains of parainfluenza 4 virus, 15 being subtype A and 3 subtype B. (2) the clinical information available from these cases. (3) a serological survey to assess the prevalence of neutralizing antibody and these viruses in England.

Evidence for a bovine origin of the polyomaviurs detected in foetal rhesus monkey kidney cells, FRhK-4 and -6

SummaryRabbit antisera to the stump-tailed macaque polyomavirus (STMV) which had been shown by immunoelectron microscopy and indirect immunofluorescence to react with the polyomavirus found in FRhK-4 cells (FRKV), also gave precipitin lines in counter-immunoelectrophoresis (CIE) and double diffusion in gel (GD) when reacted with FRKV. The reactions in GD showed identity with that of a rabbit antiserum to FRKV.Naturally occurring antibody to FRKV (anti-FRKV) was found by CIE in 48 per cent of 353 cattle, 1/106 pigs and 1/20 goats but not in any of 13 other species including 45 rhesus monkeys and 97 humans. Each of 9 anti-FRKV positive samples from cattle, the goat serum, but not the pig serum gave a line of identity with the rabbit antiserum to FRKV in GD against FRKV. Detection of anti-FRKV in colostrum deprived newborn calves and in commercial foetal calf sera (FBS) indicates that intra-uterine infection of cattle with FRKV may occur.FRKV adapted readily to growth in secondary calf kidney cultures and grew more rapidly and to higher titres than in the FRhK-4 cultures.We conclude that FRKV is probably another strain of STMV and that the natural hosts of these viruses are cattle and not primates. Evidence of intrauterine infection of cattle implies that infectious FRKV may be present in some FBS and may thus have gained entry into various susceptible cell lines, particularly primate kidney.

Human exposure to bovine polyomavirus: A zoonosis?

SummaryA competitive-type solid phase radioimmunoassay (RIA) was developed for the detection of antibody to bovine polyomavirus. Comparison of RIA and counter-immunoelectrophoresis (CIE) results on 273 cattle sera indicated that both techniques were detecting antibody of like specificity.Human sera from 256 blood donors, 219 people recently vaccinated against polio, rubella or rabies, 50 immunosuppressed patients and 472 people with various occupational exposure to cattle were tested for antibody to bovine polyomavirus, the foetal rhesus monkey kidney strain, (anti-FRKV) by RIA. Apart from one blood donor and one of 108 rabies vaccinees only those in close contact with cattle possessed anti-FRKV. Compared with 62 per cent seropositive in the natural hosts, cattle, 71 per cent of veterinary surgeons, 50 per cent of cattle farmers, 40 per cent of abattoir workers, 16 per cent of veterinary institute technical staff and 10 per cent of veterinary students were anti-FRKV positive.Our findings indicate that the theoretical hazard of FRKV infection from undetected contamination of current tissue culture derived vaccines may, in practice, be remote. Proposed wider use of primate kidney cells as substrates for new vaccines may increase this risk.

AN EVALUATION OF CYTOLOGY IN THE DIAGNOSIS OF HERPES SIMPLEX VIRUS INFECTION AND CYTOMEGALOVIRUS INFECTION OF THE CERVIX UTERI

A cytological and virological study was made to determine the incidence of herpes simplex virus (HSV) infection and cytomegalovirus (CMV) infection of the cervix uteri in 197 women attending a venereal diseases clinic. Cervical cytology was compared with virus isolation as a means of detecting these infections. Herpes simplex virus was isolated from 11 out of 186 women appropriately tested (5.9 per cent) and an additional 5 patients (2.7 per cent) showed only cytological evidence of the infection, giving a combined diagnostic rate of 8.6 per cent. Cytomegalovirus was isolated from 12 out of 145 patients suitably tested (8.3 per cent) and an inclusion‐bearing cell was identified in one of these patients. An association between CMV and multiple genital warts was noticed.

Characterization of a new polyomavirus (Polyomavirus papionis-2) isolated from baboon kidney cell cultures

SummaryViruses with papovavirus morphology were seen in fluids from baboon kidney cell cultures on three separate occasions (isolates A, B, and C). The size of the virions, 47.9 nm, placed the virus in the polyomavirus genus. It grew well in baboon kidney and Vero cells and less well in human embryo lung (HEL) fibroblasts.The virus could not be identified as the previously described baboon polyomavirus, SA 12, or as any of the other known primate polyomaviruses BK, JC or SV 40, the non-primate viruses mouse polyoma, K, rabbit kidney vacuolating virus (RKV) or bovine polyomavirus (FRKV) by immunofluorescence, immune electron microscopy or hemagglutination inhibition (HI) tests. A rabbit antiserum to the new virus (isolate A) reacted only with the three isolates and not with the other primate polyomaviruses studied.Thirteen percent of 118 wild-caught baboons (Papio anubis) had HI antibody to the new polyomavirus and 21 percent were seropositive for SA 12; only two baboons had antibody to both viruses. These results suggest that in baboons there are two antigenically distinct polyomaviruses which circulate independently. The two viruses may also be distinguished by their hemagglutinating properties: SA 12 agglutinated erythrocytes from a wider range of species but only the newly recognized polyomavirus agglutinated baboon erythrocytes.We propose that the two baboon viruses, SA 12 and the new virus, should be namedPolyomavirus papionis-1 andPolyomavirus papionis-2 respectively.

A comparison of cervical cytomegalovirus (CMV) excretion in gynaecological patients and post-partum women

SummaryCMV was isolated from the cervix of 4.2 per cent of 191 gynaecological patients and from 9.8 per cent of 51 women post-partum; all patients were attending the same general practice clinic. The CMV excretion rate was particularly high in the early post-partum period decreasing to nearly normal levels as menstruation returned. Three of 14 (21.4 per cent) post-partum patients excreted CMV before menses had restarted whereas virus was isolated from only two of 36 (5.6 per cent) women who had returned to a normal menstrual cycle. Although this difference was not statistically significant, the excretion rate early post-partum was significantly higher than in the gynaecological group (p<0.05).Five of seven excretors in the gynaecological group were in the first half of a menstrual cycle at the time of virus isolation thus suggesting that hormonal changes may lead to CMV reactivation in the genital tract. Other factors which may influence the presence of CMV in the genital tract of non-pregnant women are discussed.Three of four infants born to women excreting virus on the cervix post-partum became infected with CMV.

Prognostic significance of herpes simplex virus antibody status in women with cervical intraepithelial neoplasia (CIN)

Summary. A total of 107 women with abnormal cervical smears showing cytological changes consistent with cervical intraepithelial neoplasia (CIN) 1 or CIN 2 were kept under regular cytological, colposcopic, virological and serological surveillance for an average of 18 months (range 9 months‐3 years). Regression of the cervical lesion was noted in 31 (29%) and progression to CIN 3 in nine women (8.4%). We found a positive correlation between the presence of type 2 antibody and progression of CIN 1 and 2 to CIN 3 and a negative association with the presence of type 1 antibody and suggest the antibody status of a woman with CIN 1 or CIN 2 may provide a useful basis for follow‐up. We found no association between the outcome of the cervical lesion and active infection with herpes simplex or cytomegalovirus or any other infectious agent or sex‐related factors.

A study on the virus aetiology of mild respiratory infections in the primary school child

A survey of mild respiratory disease in a primary school was undertaken over a 2-year period to determine which of the newer respiratory viruses were responsible for these illnesses. The over-all isolation rate was low but a wide variety of viral agents was isolated. None of these caused epidemics but it is suggested they may be the cause of a low but constant absentee-rate throughout the year.