Transmission of the human T-cell lymphotropic virus type 1 (HTLV-1) seems to require cell–cell contact — the contribution to infection by cell-free HTLV-I virions is minimal. In their report in Science, Igakura et al. now show that HTLV-I is transmitted across cell–cell junctions after polarizing the cytoskeleton of the infected cell at sites of cell–cell contact.

The authors first looked at the distribution of the viral (Gag) core proteins and the glycoprotein envelope (Env) protein in isolated infected T cells, and in uninfected cells that had conjugated with HTLV-I-infected cells. After 40 minutes, they saw a strong polarization of both proteins from around the cell periphery in infected cells to the area of cell–cell contact in conjugates — a significant finding because the nucleocapsid p15 Gag protein is known to incorporate the retroviral genome into virions. In addition, another Gag protein, p19, was detected in the 'uninfected' cells of the conjugates, which might represent the initial establishment of HTLV-I infection.

Following on from the detection of p15 at the cell–cell contacts, Igakura et al. studied the localization of the HTLV-I genome. The HTLV-I nucleic acid was not polarized in single infected T cells, but it accumulated at cell–cell junctions of infected–uninfected conjugated cell pairs, similar to what was seen for the Gag and Env proteins. As was also seen for the Gag p19 protein, viral nucleic acid was later transferred to the 'uninfected' cell.

What is the cause of this asymmetrical localization? The authors noticed that polarized Gag proteins at the cell–cell junctions were frequently closely juxtaposed to a reorientated microtubule-organizing centre (MTOC). As nocodazole, which depolymerizes microtubules, inhibited the cell–cell accumulation and subsequent cell transfer of Gag, this implicates microtubule dynamics in the polarization of Gag. In addition, Igakura et al. showed that MTOC polarization occurred within the infected cell, rather than towards it.

So, when an HTLV-I-infected T cell contacts another cell, microtubule rearrangements in the infected T cells occur, and the viral genome is subsequently transferred to the recipient cell. The identity of the molecules that initiate contact and polarization is unknown; the Env protein is one candidate for fusion, being the only HTLV-I protein that is expressed on the outside of the infected cell, but HTLV-I also upregulates the expression of some adhesion molecules that could favour cell–cell transmission. Other viruses that depend on cell contact for transmission, or that are lymphotropic — such as HIV-1 — might similarly subvert normal T-cell physiology to propagate between cells.