The worldwide eradication of smallpox may, inadvertently, have helped spread HIV infection, scientists believe.
Experts say the vaccine used to wipe out smallpox offered some protection against the Aids virus and, now it is no longer used, HIV has flourished.
The US investigators said trials indicated the smallpox jab interferes with how well HIV multiplies.
But they say in the journal BMC Immunology it is too early to recommend smallpox vaccine for fighting HIV.
Kill no cure
Lead researcher Dr Raymond Weinstein, from Virginia's George Mason University, said: "There have been several proposed explanations for the rapid spread of HIV in Africa, including wars, the reuse of unsterilised needles and the contamination of early batches of polio vaccine.
"However, all of these have been either disproved or do not sufficiently explain the behaviour of the HIV pandemic."
It is a plausible explanation
Jason Warriner, clinical director for the Terrence Higgins Trust
Dr Weinstein and his colleagues believe immunisation against smallpox may go some way to explain the recent rises in HIV prevalence.
Smallpox immunisation was gradually withdrawn from the 1950s to the 1970s, following the worldwide eradication of the disease, and HIV has been spreading exponentially since then, they say.
Now, only scientists and medical professionals working with smallpox are vaccinated.
To test if the events may be linked, the researchers looked at the white blood cells taken from people recently immunised against smallpox and tested how they responded to HIV.
They found significantly lower replication rates of HIV in blood cells from vaccinated individuals, compared with those from unvaccinated controls.
The smallpox vaccine appeared to cut HIV replication five-fold.
The researchers believe vaccination may offer some protection against HIV by producing long-term alterations in the immune system, possibly including the expression of a receptor called CCR5 on the surface of white blood cells, which is exploited by the smallpox virus and HIV.
Jason Warriner, clinical director for the Terrence Higgins Trust, said: "It's impossible to say whether the withdrawal of the smallpox vaccine contributed to the initial explosion of HIV cases worldwide, but it is a plausible explanation.
"This is an interesting piece of research, and not just as a history lesson. Anything that gives us greater understanding of how the virus replicates is another step on the road towards a vaccine and, one day, a cure.
"Further studies into the role receptor cells play are needed, and even then any discoveries are likely to be just one part of the solution.
"Until we find a way to eradicate the virus from the body, the focus should remain on stopping it being passed on in the first place."