The stability of virion-associated HIV-1 RNA levels suggests that an equilibrium between HIV-1 replication rate and efficacy of immunologic response is established shortly after infection and persists throughout the asymptomatic period of the disease. Thus, defective immunologic control of HIV-1 infection may be as important as the viral replication rate for determining AIDS-free survival. Because individual steady-state levels of viremia were established soon after infection, HIV-1 RNA levels may be useful markers for predicting clinical outcome.

HIV-1 positive patients from Tanzanian villages near Shirati were examined for urinary excretion of the human polyomaviruses JC and BK using the polymerase chain reaction (PCR). BK virus (BKV) was detected in 11 of 23 individuals tested. The BKV DNA sequences were all closely related to prototype Gardner strain and BKV (DUN). In contrast, a new type of JCV, termed Type 3 [or JCV (Shi)], was identified in seven of these same 23 individuals by comparison with Type 1 and Type 2 sequences of the VP1/intergenic/T antigen region of U.S., European and Asian strains. This suggests that JCV and BKV, although closely related, have different evolutionary histories within the African population. The six BKV regulatory regions amplified all showed the archetypal configuration. However, two of the seven JCV regulatory regions showed rearrangements: a small deletion and an inverted repeat. JCV causes a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), in about 5% of AIDS patients in Europe and the U.S.A., but only one case has been reported in Africa. Our results suggest that this rarity of PML is not due to the absence of JCV in the African population.

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is the first retrovirus consistently isolated from humans. Seroepidemiologic testing for antibodies to HTLV document the following. (1) HTLV is associated with a spectrum of mature T-cell lymphoreticular neoplasms. (2) HTLV is strongly associated with clusters of adult T-cell leukemia in Japan and a related syndrome, lymphosarcoma T-cell leukemia in the Caribbean. (3) Virus-positive infections from other areas of the world share similar clinicopathologic features, with some overlap with cutaneous T-cell lymphoma (CTCL). Antibodies to HTLV are lacking in most persons with CTCL. (4) Virus-associated malignancy clusters in geographic areas where HTLV infection is prevalent, and virus positivity varies by country, region within country, age, and possibly race and sex. Although preliminary, the epidemiologic data suggest that HTLV is etiologically linked to a specific subtype of mature T-cell malignancy.

Summar-Non-malignant dermal fibroblast strains, cultured from affected members of a Li-Fraumeni syndrome (LFS) family with diverse neoplasms associated with radiation exposure. display a unique increased resistance to the lethal effects of -y-radiation. In the studies reported here. this radioresistance (RR) trait has been found to correlate strongly with an abnormal pattern of post-y-ray DNA replicative synthesis. as monitored by radiolabelled thymidine incorporation and S-phase cell autoradiography. In particular. the time interval between the y-ray-induced shutdown of DNA synthesis and its subsequent recovery was greater in all four RR strains examined and the post-recovery replication rate was much higher and was maintained longer than in normal and spousal controls. Alkaline sucrose sedimentation profiles of pulse-labelled cellular DNA indicated that the unusual pattern of DNA replication in irradiated RR strains may be ascribed to anomalies in both replicon initiation and DNA chain elongation processes. Moreover. the RR strain which had previously displayed the highest post-y-ray clonogenic survival was found to harbour a somatic (codon 234) mutation (presumably acquired during culture in vitro) in the same conserved region of the p53 tumoursuppressor gene as the germline (codon 245) mutation in the remaining three RR strains from other family members. thus coupling the RR phenotype and abnormal post--y-ray DNA synthesis pattern with faulty p53 expression. Significantly. these two aberrant radioresponse end points. along with documented anomalies in c-mc and c-raf-l proto-oncogenes. are unprecedented among other LFS families carrying p53 germline mutations. We thus speculate that this peculiar cancer-prone family may possess in its germ line a second, as yet unidentified, genetic defect in addition to the p53 mutation

These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.