A cell system was developed for the reproducible detection of human T-lymphotropic retroviruses (HTLV family) from patients with the acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that frequently precede AIDS (pre-AIDS). The cells are specific clones from a permissive human neoplastic T-cell line. Some of the clones permanently grow and continuously produce large amounts of virus after infection with cytopathic (HTLV-III) variants of these viruses. One cytopathic effect of HTLV-III in this system is the arrangement of multiple nuclei in a characteristic ring formation in giant cells of the infected T-cell population. These structures can be used as an indicator to detect HTLV-III in clinical specimens. This system opens the way to the routine detection of HTLV-III and related cytopathic variants of HTLV in patients with AIDS or pre-AIDS and in healthy carriers, and it provides large amounts of virus for detailed molecular and immunological analyses.

https://science.sciencemag.org/content/sci/224/4648/497.full.pdf

Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS

Classification of Papillomaviruses (PVs) Based on 189 PV Types and Proposal of Taxonomic Amendments

In cats, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or T-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I can cause T-cell proliferation and leukemia. The subgroup HTLV-II also induces T-cell proliferation in vitro, but its role in disease is unclear. Viruses of a third subgroup of human T-lymphotropic retroviruses, collectively designated HTLV-III, have been isolated from cultured cells of 48 patients with acquired immunodeficiency syndrome (AIDS). The biological properties of HTLV-III and immunological analyses of its proteins show that this virus is a member of the HTLV family, and that it is more closely related to HTLV-II than to HTLV-I. Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.

https://science.sciencemag.org/content/sci/224/4648/506.full.pdf

Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS

Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the viruses in cultured cells. For instance, it has not been established whether the major capsid protein L1 alone is sufficient for virus particle assembly. In addition, it is not known whether L1, L2 (the minor capsid protein), or both present the immunodominant epitopes required for induction of high-titer neutralizing antibodies. We have expressed the L1 major capsid proteins of bovine papillomavirus type 1 and human papillomavirus type 16 in insect cells via a baculovirus vector and analyzed their conformation and immunogenicity. The L1 proteins were expressed at high levels and assembled into structures that closely resembled papillomavirus virions. The self-assembled bovine papillomavirus L1, in contrast to L1 extracted from recombinant bacteria or denatured virions, also mimicked intact bovine papillomavirus virions in being able to induce high-titer neutralizing rabbit antisera. These results indicate that L1 protein has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent papillomavirus infection.

https://www.pnas.org/content/pnas/89/24/12180.full.pdf

Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic.

A highly T-lymphotropic virus was isolated from cats in a cattery in which all the animals were seronegative for feline leukemia virus. A number of cats in one pen had died and several had an immunodeficiency-like syndrome. Only 1 of 18 normal cats in the cattery showed serologic evidence of infection with this new virus, whereas 10 of 25 cats with signs of ill health were seropositive for the virus. Tentatively designated feline T-lymphotropic lentivirus, this new feline retrovirus appears to be antigenically distinct from human immunodeficiency virus. There is no evidence for cat-to-human transmission of the agent. Kittens experimentally infected by way of blood or plasma from naturally infected animals developed generalized lymphadenopathy several weeks later, became transiently febrile and leukopenic, and continued to show a generalized lymphadenopathy 5 months after infection.

http://science.sciencemag.org/content/sci/235/4790/790.full.pdf

Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome.

A virus-like particle associated with leukemia (lymphosarcoma).

The bladder cancer syndrome that often accompanies chronic enzootic hematuria in cattle grazing on pastures infested by bracken fern has been experimentally reproduced in animals fed a diet of bracken. The experimentally induced tumors were histologically and pathologically indistinguishable from the naturally occurring ones and comprised two main types: (a) carcinoma of the urothelium identical to that seen in humans; and (b) hemangioendotheliomas of the subjacent capillaries. Often the two types of tumor occurred together in the same bladder. In animals experimentally immunosuppressed with azathioprine "bracken type" hemangiomas developed in the bladder lining. DNA of bovine papillomavirus (BPV) type 2 was found in 46% (7 of 15) of the natural cancer cases and in 69% (9 of 13) of the experimentally induced lesions, independently of histological type and including the hemangiomas of the azathioprine-treated animals, suggesting a close association between BPV and bovine bladder neoplasia. Moreover, BPV-2 DNA was found in experimental animals that had not been inoculated with BPV at all or had been inoculated with a different BPV type and had been kept in isolation, suggesting that BPV can persist in a latent state and be activated when the animal is exposed to the bracken cocarcinogens and to immunosuppressants.

https://cancerres.aacrjournals.org/content/canres/52/24/6898.full.pdf

Association of Bovine Papillomavirus Type 2 and Bracken Fern with Bladder Cancer in Cattle

Horizontal Transmission of Leukemia Virus and Leukemia in the Cat

Transmission experiments with leukemia (lymphosarcoma).

Papillomaviruses are ubiquitous DNA viruses affecting humans and animals and causing a variety of tumours of mucosal and cutaneous epithelia. Some of these lesions, particularly those affecting mucosal epithelia, can progress to squamous cell carcinomas. Prevention or cure of viral infection would ultimately lead to a decrease in the incidence of papillomavirus-associated cancers. Using recombinant proteins, we have developed prophylactic and therapeutic vaccines against bovine papillomavirus type 4, a mucosal papillomavirus implicated in cancer of the alimentary canal in cattle; similar possibilities exist for the human mucosal papillomaviruses.

William F.H. Jarrett

Papers

A virus-like particle associated with leukemia (lymphosarcoma).

Association of Bovine Papillomavirus Type 2 and Bracken Fern with Bladder Cancer in Cattle

Horizontal Transmission of Leukemia Virus and Leukemia in the Cat

Transmission experiments with leukemia (lymphosarcoma).

Prophylactic and therapeutic vaccination against a mucosal papillomavirus