Healthy Skin of Many Animal Species Harbors Papillomaviruses Which Are Closely Related to Their Human Counterparts

Papillomaviruses associated with clinical symptoms have been found in many vertebrate species. In this study, we have used an L1 gene consensus PCR test designed to detect a broad spectrum of human skin papillomaviruses to analyze swab samples from healthy skin of 111 animals belonging to 19 vertebrate species. In eight of the species, papillomavirus DNA was found with the following prevalences: chimpanzees, 9 of 11 samples positive; gorillas, 3 of 4; long-tailed macaques, 14 of 16; spider monkeys, 2 of 2; ruffed lemurs, 1 of 2; cows, 6 of 10; European elks, 4 of 4; aurochs, 1 of 1. In total, 53 new putative animal papillomavirus types were found. The results show that skin papillomaviruses can be detected in healthy skin from many different animal species and are sufficiently related genetically to their human counterparts to be identified by a human skin papillomavirus primer set (FAP59 and FAP64)

A microcarrier cell culture system for large scale production of hepatitis A virus

Hepatitis A virus (HAV) was isolated from human faeces using a fetal rhesus monkey kidney cell line (Frhk-4). Infectious medium from passage 12 was used to inoculate a large (5000 cm2) microcarrier cell culture maintained in suspension. The microcarriers used were swollen, collagen-coated dextran beads on which it was easy to propagate Frhk-4 cells. Intra- and extra-cellular virus levels were assayed and compared with conventional cultures in 25 cm2 plastic flasks. The results show that virus production per cell was similar in both systems. The number of cells per area unit in confluent cultures was initially lower in the microcarrier culture but subsequently increased. Two to three weeks post inoculation the virus yield per area unit in the microcarrier system was half of that of the conventional culture. The lower cell density per area unit in the microcarrier system was compensated by the large growth area that could be maintained in a single vessel and the total production of virus was substantial. Weekly harvests of medium with HAV antigen titres around 10(-2) contained antigenic material sufficient for several thousands of anti-HAV IgM tests. Propagation of HAV in microcarrier cell cultures thus seems a safe and simple way to produce large amounts of HAV

Increased occurrence of hepatitis A with cyclic outbreaks among drug addicts in a Swedish community

To determine the prevalence of antibodies to Hepatitis A virus (anti-HAV) among drug addicts, sera collected in a Swedish city during a ten-year period from 234 drug addicts with acute hepatitis B were tested for anti-HAV. The results were compared with the normal population, where only 3.8% of those born after 1950 were anti-HAV-positive. In individuals born between 1941 and 1965, 8.2% in the normal population and 30.2% of the drug addicts were anti-HAV-positive (p less than 0.001). The level of immunity to hepatitis A among drug addicts ranged from 7.7% to 60% during the ten-year period. Low levels of immunity were seen in the years preceeding outbreaks of hepatitis A among drug addicts. These outbreaks occurred in a cyclic pattern. Higher levels of immunity were seen after each outbreak

Enhancement of hepatitis A propagation in tissue culture with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole

The adenosine analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) was found to increase the production of hepatitis A (HAV) antigen in two monkey kidney cell lines (Frhk-4 and Vero cells). DRB, a known inhibitor of the synthesis of messenger RNA, caused moderate changes in cell morphology. However, Frhk-4 cells could be maintained for several weeks at 80 microM of DRB, the concentration that caused maximal enhancement on HAV. DRB should be present from about the time of virus inoculation and its strongest effect was seen at low multiplicities of infection. Using radioimmunofocus assay it could be shown that DRB increased the amount of infectious virus. DRB treatment was applied in primary isolation of HAV from feces. In nine of ten strains HAV antigen expression was strongly increased and in six of the ten strains infectivity of harvested material increased by one 10log or more. DRB thus seems to be a useful enhancer of HAV growth in tissue culture

Influence of twenty potentially antiviral substances on in vitro multiplication of hepatitis A virus

A multiwell tissue culture system was developed to study the influence of various substances on hepatitis A virus (HAV) propagation. A panel of 20 substances of different structure types, each with known effect against at least some viruses, was studied at a concentration of 100 microM. Three substances showed reproducible inhibition. The strongest inhibitor, arabinosylcytosine, also produced cytotoxic changes in cells down to a concentration of 1 microM, and its effect was considered as nonspecific. Amantadine and ribavirin showed a moderate effect at 100 microM. A stronger inhibition was seen at 250 and 500 microM, doses that are toxic and impractical for clinical use. Although no promising candidates for antiviral treatment of hepatitis A have emerged from the present study, the assay model described here would seem useful in the screening of substances with inhibitory effects on HAV

Post-transfusion hepatitis type non-A, non-B in southern Sweden: occurrence and clinical significance

Two prospective studies of the occurrence and clinical significance of post-transfusion hepatitis non-A, non-B were performed in Malmo, Sweden. In both studies, patients of a broad clinical spectrum were followed up 6 and 12 weeks after transfusion. In a 7 week study from 1983, hepatitis non-A, non-B occurred in 9/173 transfused patients (5.2%) versus 1/203 untransfused controls (0.5%) (p less than 0.01). In a 6 month study from 1984-85, the incidence of hepatitis non-A, non-B had declined to 2.4% (18/739 transfused patients). The mean number of transfused units was about 5 in both studies and most patients had subclinical disease. Despite similar transfusion volumes to patients above or below 70 years of age, hepatitis non-A, non-B was predominantly seen among patients less than 70 years. In the 1984-85 study, hepatitis non-A, non-B incidence was 1.2% in recipients greater than or equal to 70 years, 3.4% in recipients less than 70 years and 4.5% in recipients less than 40 years. One year after the initial hepatitis non-A, non-B episode, 4/18 patients (22%) had biochemical signs of chronic hepatitis

General Acquisition of Human Papillomavirus Infections of Skin Occurs in Early Infancy

The human skin papillomaviruses (HPVs) represent a group of ubiquitous viruses detected at a high prevalence in the normal skin of healthy adults. In the present study, we analyzed skin swab samples from babies during their first days of life and from infants at various ages up to age 4 years. Specimens from their parents and, for the newborn babies, environmental samples were also investigated. HPV DNA was already detected on the day of birth in samples from 2 of the 16 babies, and 45% of the samples from the babies were positive for HPV in the days following birth. Seventy-seven percent of the skin samples collected from the mothers were HPV DNA positive. The prevalence of HPV DNA among children from the ages of 1 month to 4 years varied between 50 and 70%. The HPV DNA sequences detected revealed a great diversity of genotypes and putative genotypes. Among 115 samples from 38 infants and 31 parents and 7 environmental samples, a total of 73 HPV types or putative types were isolated. Of these, 26 putative HPV types have not been described before. Our data suggest that asymptomatic HPV infections of normal skin are acquired very early in infancy and are caused by a great multiplicity of HPV types

Antibody to hepatitis-C-virus-related proteins in sera from alanine-aminotransferase-screened blood donors and prospectively studied recipients

A prospective study of posttransfusion non-A, non-B hepatitis was conducted in Malmo, Sweden, in 1984-1985, in which donors were alanine aminotransferase (ALT) screened but not ALT selected. Among 741 patients studied at 0, 6, and 12 weeks after transfusion, 13 developed non-A, non-B hepatitis, and these were further followed up. Stored sera from the 13 hepatitis patients and their 123 donors were tested for anti-hepatitis C virus (HCV) by ELISA and if positive, analyzed by recombinant immunoblot assay (RIBA). All ALT-elevated blood units (n = 301) and a similar number of ALT-normal units were also tested. Only 4/13 patients with non-A, non-B hepatitis seroconverted to anti-HCV, all with ALT peaks greater than 10 times the upper normal. All seroconversions occurred within 5 months after transfusion and could be confirmed by RIBA. Hepatitis C in recipients occurred both after transfusion of blood that was strongly positive, weakly positive, and/or negative for anti-HCV by ELISA. In donors grouped by ALT levels, the anti-HCV prevalence varied between 0.4 (normal ALT) and 14% (ALT elevated greater than or equal to 2 times). Of the total of 9 donor units positive by ELISA, only 5 were confirmed by RIBA. Of the 5 recipients of the RIBA-positive blood units, 3 went into hepatitis, 1 remained normal at 10.5 weeks, and 1 showed a slight, transient ALT elevation at week 12. The recipients of ELISA-positive but RIBA-negative blood remained healthy