Human T-lymphotropic virus type III (LAV, HTLV-III) is aetiologically linked to acquired immune deficiency syndrome (AIDS) and persistent general lymphadenopathy (PGL). Specific radioimmunoassays (RIA), enzyme-linked assays, immunofluorescence assays (IFA) and immunoblotting techniques are being used widely to detect serum antibodies to HTLV-III in infected patients and in those at risk of infection. However, these assays do not functionally identify those antibodies that neutralize the infectivity of the virus. We have used three methods of titrating serum neutralizing factors: inhibition of syncytium induction, neutralization of envelope pseudotypes of vesicular stomatitis virus (VSV) and reduction of infectivity of HTLV-III for a cell line permissive to virus replication. We report here that sera from subjects in various disease categories possess only low-level neutralizing activity, even when antibodies to viral membrane antigens are present in high titre. Envelope pseudotypes prepared from four HTLV-III isolates made in three different countries are equally sensitive to neutralization by positive sera, including sera from patients yielding two of the virus isolates.

HTLV-producing T-cell lines induce cell fusion when co-cultivated with a wide variety of indicator cells, suggesting that HTLV envelope antigens interact with the membranes of many cell types. Serum antibodies from adult T-cell lymphoma-leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and Japanese ATL patients inhibited cell fusion induced by American and Japanese HTLV isolates equally well. No serological cross-inhibition of syncytium induction was found between HTLV and bovine leukosis virus, Moloney murine leukemia virus and simian sarcoma-associated virus. A simple syncytium inhibition test in microtiter plates has been developed to provide a rapid screen for antibodies presumed to be specific to HTLV envelope glycoproteins.

Human T-cell leukemia virus (HTLV), American PL isolate, was transmitted by cocultivation and by cell-free filtrates to a nonlymphoid human osteogenic sarcoma (HOS) cell line, designated HOS/PL, but not to nine other lines bearing receptors for HTLV. HOS and HOS/PL cells are not dependent on interleukin-2 and do not express interleukin-2 receptors that are recognized by anti-Tac monoclonal antibody. HTLV released by the Japanese MT2 cell line was also transmitted to HOS cells. The infected HOS cells release substantial titers of progeny HTLV which is antigenically indistinguishable from parental virus and is able to transform T cells.

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