The role of human endogenous retroviruses in melanoma.

Sequencing of the human genome has established that our DNA harbours many endogenous retrovirus (ERV) sequences, remnants of ancestral exogenous retroviral infections fixed in the germline DNA. In recent years, human ERVs (HERVs) have been implicated in melanomagenesis. Retrovirus-like particles and the expression of HERV mRNA and proteins have been demonstrated in melanoma tissue. In addition, antibodies to HERV proteins have been observed in patients with melanoma. In vitro and mouse models have provided fascinating insights into the potential mechanisms of HERVs in melanomagenesis. This review considers the evidence associating HERVs with melanoma.

HERV-K: the biologically most active human endogenous retrovirus family.

The human genome contains a wide variety of endogenous retrovirus-like sequences. The human endogenous retrovirus type K (HERV-K) family comprises 30-50 members per haploid genome in humans and is highly conserved in Old World monkeys and apes. Some proviruses are displaying open reading frames (ORF) with coding capacity for viral particles. HERV-K sequences most likely code for the previously described human teratocarcinoma-derived virus (HTDV) and correlated expression of HERV-K Gag has been demonstrated by immunoelectron microscopy studies. Protease, but not yet reverse transcriptase (RT), enzymatic activity was demonstrated for recombinant HERV-K proteins. However, an ultrasensitive RT assay revealed specific polymerase activity associated with the HTDV particles. HERV-K transcription is specifically regulated by viral long terminal repeats and RNA is expressed at low steady-state levels in a variety of human tissues and tumours. In teratocarcinoma cell lines, HERV-K is highly expressed in a complex pattern showing full-length as well as subgenomic envelope (env) and two alternatively spliced small transcripts. The doubly spliced 1.8-kb mRNA codes for cORF protein which resembles Rev of HIV-1 and is located in the nucleolus. In addition, the cORF sequence acts as a leader and is essential for effective expression of glycosylated HERV-K Env protein. Although HERV-K sequences code for all necessary retroviral proteins, infectious particles could not yet be demonstrated. The putative implication of HERV sequences in pathophysiological processes, for example, testicular malignancies, remains to be elucidated.

Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infections. Centers for Disease Control, U.S. Department of Health and Human Services.

Infection with the human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) [now human immunodeficiency virus] can manifest as a spectrum of conditions ranging from severe immunodeficiency to asymptomatic infection. Because of the rapid growth of knowledge about this virus, there is a need for a system to classify patients with the various manifestations of infection. The presented system comprises four mutually exclusive groups: I, acute infection; II, asymptomatic infection, III, persistent generalized lymphadenopathy; and IV, other HTLV-III/LAV disease (with five subgroups, A to E, and two subcategories, C-1 and C-2). The classification should be useful in disease reporting and surveillance, epidemiologic studies, prevention and control activities, and public health policy and planning.

Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infections.

PIP: This article presents a classification system for patients with the spectrum of clinical and laboratory findings attributable to human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). This classification system is primarily for public health purposes, including disease reporting and surveillance, epidemiologic studies, prevention and control activities, and public health policy and planning. The system classifies the manifestations of HTLV-III/LAV infection into 4 groups: I) patients with transient signs and symptoms that appear at the time of, or shortly after, initial infection with HTLV-III/LAV as identified by laboratory studies; II) patients with no signs or symptoms of HTLV-III/LAV infection, who in turn can be subclassified on the basis of whether hematologic and/or immunologic studies have been done and whether results are abnormal; III) patients with persistent generalized lymphadenopathy at 2 or more extra-inguinal sites persisting for more than 3 months in the absence of a condition other than HTLV-III/LAV infection to explain these findings; and IV) patients with clinical symptoms and signs of HTLV-III/LAV infection other than or in addition to lymphadenopathy. Patients in Group IV are further categorized into 5 subgroups: A) constitutional disease, B) neurologic disease, C) secondary infectious disease, D) secondary cancers, and E) other conditions resulting from HTLV-III/LAV infection. This classificatory system will require periodic revision as new information about HTLV-III/LAV infection is accumulated. Patients whose clinical presentations fulfill the surveillance definition of acquired immunedeficiency syndrome (AIDS) should be classified in Group IV.^ieng

A classification of HTLV-III infection based on 75 cases seen in a suburban community.

Since 1981, 75 patients have been seen at our hospital with human T-cell lymphotropic virus type III (HTLV-III) infection. We have classified their clinical presentation into Groups 0 to 6. Groups 0 to 3 all have antibody to the Mr 41,000 protein of HTLV-III. Group 0 has no evident disease (9 patients), Group 1 has lymphadenopathy with or without exaggerated infection (16 patients), Group 2 has persistent lymphadenopathy with chronic hepatitis B surface antigenemia or profound hypergammaglobulinemia (7 patients), Group 3 has oral candidiasis with or without lymphadenopathy (7 patients). In Group 4 are acquired immunodeficiency syndrome (AIDS) adults or children (32 patients). Group 5 is a special classification for immunocompromised patients. Group 6 patients have lymphomas and Mr 41,000 protein antibody. Four children were classified separately. Three patients in Group 3 developed Group 4 disorders (AIDS). Four patients in Group 4 developed Group 6 disorders. HTLV-III infection spread in families (8 of 36), all from infected mothers to children. In 17 sexual partners, 6 were found to be infected. Five of 6 infected partners were homosexuals. We saw an inordinate number of transfusional AIDS (4 of 29) and 1 of 46 other disorders. Two infants also presented with severe intracranial defects, one with microcephaly and one with cranial calcifications and lucency. HTLV-III is spreading with alarming speed.