J. van der Noordaa

Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS.

Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and persisted throughout the course of the disease. This antigenaemia was accompanied by the disappearance of IgG antibody reactivity to the major HIV core protein p24. In none of the 12 others, who all remained without serious disease, were serum concentrations of HIV antigen detected, except on one occasion in one man. All their serum samples showed strong IgG antibody reactivity to p24. Nine children who were infected with HIV in 1981 by plasma transfusion from a single donor were also followed up for HIV antigenaemia. HIV antigen was almost constantly present in the serum (26 of 28 samples) of five children who developed AIDS related complex or AIDS and less often in the serum (four of 10 samples) of four children who remained free of symptoms. The two children who developed AIDS showed a virtual absence of antibody reactivity to p24. These results indicate that increased HIV gene expression is a contributing factor to the development of AIDS and also provide evidence for a switch from latent to active HIV infection.

Distinct IgG recognition patterns during progression of subclinical and clinical infection with lymphadenopathy associated virus/human T lymphotropic virus

Longitudinal IgG recognition patterns of viral proteins were studied in 15 men who had seroconverted for lymphadenopathy associated virus/human T lymphotropic virus (LAV/HTLV-III). Antibodies to the major viral core protein p24, which is a cleavage product of the gag gene encoded precursor protein pr55, appeared first. These were soon followed by antibodies to pr55 and more gradually by antibodies to the other gag gene encoded cleavage product p18, the env gene encoded transmembrane glycoprotein gp41, the env gene encoded glycoproteins gp65 and gp110, and the putative pol gene product p33. In 13 subjects who remained healthy the reactivity to the different proteins increased or stabilised with time, while in two men who developed acquired immune deficiency syndrome (AIDS) the reactivity, most noticeably to gag encoded proteins, diminished before or at the onset of symptoms.

Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia.

One hundred and ninety eight men seropositive for human immunodeficiency virus (HIV) antibody and 58 HIV antibody seroconverters were studied for an average of 19.3 (SEM 0.5) months to assess the relation between HIV antigenaemia and the risk of developing the acquired immune deficiency syndrome (AIDS) and AIDS related complex. Forty (20.2%) of the 198 HIV antibody seropositive men were antigen positive at entry and remained so during follow up. Eight (13.8%) of the 58 HIV antibody seroconverters and 20 (12.7%) of the remaining 158 HIV antibody seropositive men became antigen positive during follow up, resulting in an end point attack rate for HIV antigenaemia of 14.3%. AIDS related complex was diagnosed in 25 (15.8%) of the HIV antigen negative men and in 14 (20.7%) of the HIV antigen positive men. AIDS was diagnosed in 15 men, resulting in an end point attack rate for AIDS of 23.9% in the HIV antigen positive group and 1.3% in the antigen negative group. HIV antibody seropositive men without symptoms but with persistent HIV antigenaemia are at increased risk of developing AIDS and AIDS related complex.

Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex.

De novo synthesis in the central nervous system of IgG antibodies to human T cell lymphotropic virus type III (HTLV-III) (lymphadenopathy associated virus) was shown in seven of 10 seropositive men who had syphilis but not the acquired immune deficiency syndrome (AIDS) or AIDS related complex. None of these men showed neurological symptoms when the serum and cerebrospinal fluid were collected. Pleocytosis was present in all 10. Of the seven men who showed evidence of intrathecal synthesis of antibodies, five had increased total concentrations of IgG and four had oligoclonal IgG bands in their cerebrospinal fluid. Oligoclonal bands were also present in one man who did not have any antibodies. Longitudinal study of one man showed that seroconversion preceded intrathecal synthesis of antibody specific to HTLV-III. The appearance of antibody in the cerebrospinal fluid was accompanied by a transient rise in mononuclear cell count and the appearance of oligoclonal bands. The presence of clones of B cells specific to HTLV-III in the central nervous system of these patients without persisting neurological symptoms suggests that HTLV-III enters the central nervous system in the early stages of infection.

Uniformity of the Splicing Pattern of the E6/E7 Transcripts in Human Papillomavirus Type 16-transformed Human Fibroblasts, Human Cervical Premalignant Lesions and Carcinomas

We utilized the RNA polymerase chain reaction (PCR) to analyse the transcripts of the E6/E7 open reading frames of human papillomavirus type 16 (HPV-16). Total RNA was isolated from 14 cervical squamous carcinomas, nine cervical intraepithelial neoplasias and from human fibroblasts transformed with different HPV-16 constructs. In all specimens two spliced transcripts were detected. Sequence analysis of the cloned PCR products showed that both transcripts were generated by splicing out an intron in E6, from nucleotides (nt) 226 to 409 in one transcript and from nt 226 to 526 in the other. The major transcript present in all RNA specimens had the smallest intron in E6. The RNA PCR described here is the method of choice for analysing splice and donor sites in tissue specimens where a limited amount of RNA is available. Results obtained with transformed cells revealed no difference in splicing whether HPV-16 was controlled by its homologous promoter or by a heterologous promoter, the Rous sarcoma virus long terminal repeat.

Impact of HIV antibody testing on changes in sexual behavior among homosexual men in The Netherlands.

Between October 1984 and May 1986, 746 homosexual men, living in and around Amsterdam, The Netherlands, were surveyed at three consecutive six months periods regarding their sexual behavior. At the start of the study all subjects, of whom 234 (31 per cent) were HIV-Ab seropositive, were informed about their HIV antibody status. Seropositives initially reported more sexual partners than seronegatives; they also showed a greater reduction in the number of sexual partners and the number of partners with whom all forms of sexual practices were performed than did seronegatives. In both groups subjects were more likely to terminate orogenital intercourse than anogenital intercourse and masturbation.

The complete nucleotide sequence of bovine polyomavirus.

The complete sequence of the genome of bovine polyomavirus (BPyV), formerly known as the CK isolate of the stump-tailed macaque virus, is presented. The genomic organization of BPyV is similar to that of the non-rodent polyomaviruses. With a genome size of 4697 bp, BPyV has the smallest polyomavirus genome known so far. When compared to simian virus 40 (SV40), the shortness of the BPyV genome is due mainly to differences in the coding capacity of the BPyV early region. The first exon of the proposed large T antigen encodes only 35 amino acids; also, a coding region corresponding to the C-terminal 64 amino acids of the SV40 large T antigen is absent in BPyV. It is proposed that the nucleotide sequence encompassing the small t antigen coding sequence contains an intron sequence of 71 nucleotides. Together the two exon sequences encode a 124 amino acid protein. We conclude that this may be the first example of a polyomavirus that has a small t antigen which is translated from two exon sequences. The enhancer region of BPyV does not show homology to the SV40 enhancer sequences. An agnogene is present with a coding capacity of 118 amino acid residues. The highest degree of homology to SV40 and PyV is present in the VP1 molecule.

Infectivity, oncogenicity and transforming ability of BK virus and BK virus DNA.

Summary The human papovavirus, BK, appeared weakly oncogenic in newborn hamsters and was able to induce in vitro transformation of rat kidney cells. The infectivity of BK virus DNA was determined by employing the DEAE-dextran method. In human embryonic cells the infectivity was approx. 105 p.f.u./µg of DNA. The transforming ability of BK virus in primary rat kidney cells was measured by employing the calcium method and appeared to vary from 1 to 10 foci per µg of DNA.

Localization of human papillomavirus type 16 DNA using the polymerase chain reaction in the cervix uteri of women with cervical intraepithelial neoplasia

The localization of human papillomavirus type 16 (HPV-16) DNA throughout the cervix uteri of women with cervical intraepithelial neoplasia (CIN) was studied by utilizing the polymerase chain reaction technique directly on histologically defined sections of paraffin-embedded cervical tissue obtained by conizations. HPV-16 DNA was detected only in the sections that contained CIN lesions and/or koilocytes. No HPV-16 DNA was detected in sections that contained only normal epithelium. This is in accordance with HPV-16 playing a role in the development of CIN lesions.

Infectivity and Molecular Weight of Varicella-Zoster Virus DNA

Summary Trypsin treatment of varicella-zoster virus infected cells resulted in release of infective cell free virus in the supernatant. Varicella-zoster virus DNA could be isolated from purified virus. The DNA was infective and the mol. wt. was approx. 80 × 106 as determined by length measurements.