Enigmatic virus may hold clues to chronic infection

25 June 2003 12:00 GMT

by Alex Venter

New details are emerging on the mechanisms of infection by human T lymphotropic virus type 1 (HTLV-1), a distant cousin of HIV. HTLV-1 infects 20 million people worldwide and is endemic in Brazil, the Caribbean and southern Japan.

HTLV-1 can cause adult T-cell leukemia and an inflammatory disease similar to multiple sclerosis, although only about 5% of those infected show such clinical symptoms. Charles Bangham of Imperial College London says that HTLV-1 makes a good model for studying chronic infectious viruses such as HIV, hepatitis B and C, and cytomegalovirus. His data were presented at an annual conference on retroviruses, held last month in San Francisco.

Bangham and his colleagues put HTLV-1-infected T cells under the confocal microscope. The researchers tracked the movement of the cell's 'skeleton,' which aggregated next to a cell-to-cell junction - a process called polarization. "We don't yet know the molecular details of the mechanism, but what we observed was that the virus seems to cause the polarization," said Bangham.

Polarization occurs normally in T-cells that are sending chemical messages to one another. HTLV-1 appears to use polarization to directly infect neighboring cells. "[It is] a very clever evolutionary trick," said Bangham, allowing HTLV-1 "to subvert the normal T-cell physiology."

Unpublished data now suggests that HIV may use a similar strategy. Quentin Sattentau, who is currently based at the University of Oxford, has found that, at times, HIV may be transmitted directly from cell to cell without producing extracellular, enveloped virus particles.

Cell to cell transmission is a good survival strategy because it is efficient, says Bangham. It saves the virus from wasting lots of particles, he said "which go off like fish's eggs in the sea." More importantly, he notes, the virus is partly hidden from the immune system when it is inside T-cells.

The fact that, much of the time, HTLV-1 does not cause overt disease, continues to ensure the survival of the virus, because it can be passed unwittingly from person to person via breast milk, contaminated blood and through sexual contact. "[HTLV-1] is very well adapted to its host," said Bangham, "it's not a recent acquisition."

Edward Murphy, chair of the recent HTLV conference, wonders if HIV-2 will similarly persist due to reduced virulence. "HIV, being a more recent virus, will eventually settle down . . . and become much less pathogenic [like HTLV-1]," predicted Murphy.

Why some people, but not others, are able to mount a strong T-cell response against HTLV-1 and remain asymptomatic carriers is a puzzle. Bangham's research team has identified certain genetic factors that play a role, although based on this evidence, said Bangham, "We haven't got all the explanation."

26 June 2003


Enigmatic virus may hold clues to chronic infection 25 June 2003 12:00 GMT by Alex Venter New details are emerging on the mechanisms of infection by human T lymphotropic virus type 1 (HTLV-1), a distant cousin of HIV. HTLV-1 infects 20 million people worldwide and is endemic in Brazil, the Caribbean and southern Japan. HTLV-1 can cause adult T-cell leukemia and an inflammatory disease similar to multiple sclerosis, although only about 5% of those infected show such clinical symptoms. Charles Bangham of Imperial College London says that HTLV-1 makes a good model for studying chronic infectious viruses such as HIV, hepatitis B and C, and cytomegalovirus. His data were presented at an annual conference on retroviruses, held last month in San Francisco. Bangham and his colleagues put HTLV-1-infected T cells under the confocal microscope. The researchers tracked the movement of the cell's 'skeleton,' which aggregated next to a cell-to-cell junction - a process called polarization. "We don't yet know the molecular details of the mechanism, but what we observed was that the virus seems to cause the polarization," said Bangham. Polarization occurs normally in T-cells that are sending chemical messages to one another. HTLV-1 appears to use polarization to directly infect neighboring cells. "[It is] a very clever evolutionary trick," said Bangham, allowing HTLV-1 "to subvert the normal T-cell physiology." Unpublished data now suggests that HIV may use a similar strategy. Quentin Sattentau, who is currently based at the University of Oxford, has found that, at times, HIV may be transmitted directly from cell to cell without producing extracellular, enveloped virus particles. Cell to cell transmission is a good survival strategy because it is efficient, says Bangham. It saves the virus from wasting lots of particles, he said "which go off like fish's eggs in the sea." More importantly, he notes, the virus is partly hidden from the immune system when it is inside T-cells. The fact that, much of the time, HTLV-1 does not cause overt disease, continues to ensure the survival of the virus, because it can be passed unwittingly from person to person via breast milk, contaminated blood and through sexual contact. "[HTLV-1] is very well adapted to its host," said Bangham, "it's not a recent acquisition." Edward Murphy, chair of the recent HTLV conference, wonders if HIV-2 will similarly persist due to reduced virulence. "HIV, being a more recent virus, will eventually settle down . . . and become much less pathogenic [like HTLV-1]," predicted Murphy. Why some people, but not others, are able to mount a strong T-cell response against HTLV-1 and remain asymptomatic carriers is a puzzle. Bangham's research team has identified certain genetic factors that play a role, although based on this evidence, said Bangham, "We haven't got all the explanation."