Men's testicles 'HIV hiding spot'

[Guest guest]

Men's testicles 'HIV hiding spot'

(The abstract of the paper, which is the basis of this BBC news

article " Susceptibility of Human Testis to Human Immunodeficiency

Virus-1 Infection in Situ and in Vitro " follows the news text.

Moderator)

HIV can dodge destruction by powerful antiretroviral drugs by hiding

out in the testicles, scientists say. The French work in the American

Journal of Pathology suggests the gonads provide an ideal environment

for the Aids virus to replicate itself.

Evidence shows even the best antiretrovirals find it difficult to

penetrate the testes. This may explain why HIV can still be found in

the semen of men on drugs that successfully clear their blood of it.

Infected semen

The team say their work could help with the development of new

antiretrovirals that can target HIV in the gonads. This is

particularly important given that sexual transmission is one of the

main ways HIV is spread from person to person. According to the most

recent World Health Organization data, 39.5 million people are

infected with HIV.

Dr Nathalie Dejucq-Rainsford and colleagues from Rennes University

examined testicular tissue. They discovered certain immune cells had

the necessary machinery to allow HIV safe passage.

These cells, called macrophages, had all of the required receptors -

CD4, CXCR4, CCR5, and DC-SIGN - to bind HIV. Closer inspection

revealed HIV was making copies of itself within the testicular

macrophages.

When they took some more of the testicular tissue and grew it in the

lab, they found HIV was able to thrive there and was capable of

infecting other cells.

The study authors explained: " Although highly active antiretroviral

therapy (HAART) may achieve undetectable virus levels in the blood,

virus replication in the testis may permit continued spread of the

virus.

" The infected cells appeared to be testicular macrophages located

within the interstitial tissue. "

A spokesman from Avert said: " It has long been known that the testes

act as a reservoir for HIV, but this is the first piece of research

that really demonstrates exactly why this is the case.

" If methods developed by these researchers were to result in new

products that could suppress HIV replication within the testes, then

this would represent an exciting advance in prevention technology.

" However, it seems unlikely that these would be available any time in

the foreseeable future, so for the moment, condoms remain the best

method of preventing HIV during sexual intercourse. "

__________________

Susceptibility of Human Testis to Human Immunodeficiency Virus-1

Infection in Situ and in Vitro

Roulet*, Anne-Pascale Satie*, Annick Ruffault , Le

Tortorec*, Hélène Denis*, Odile Guist'hau , Jean-Jacques Patard ,

Nathalie Rioux-Leclerq , Janine Gicquel , Bernard Jégou* and Nathalie

Dejucq-Rainsford*

From INSERM U625,* Rennes; University of Rennes I, Groupe d'Etude de

la Reproduction chez l'Homme et les Mammifères, IFR 140, Campus de

Beaulieu, Rennes; and the Unité de Rétrovirologie and Services

d'Urologie and d'Anatomo-Pathologie, Centre Hospitalier

Universitaire Régional Pontchaillou, Rennes, France

(American Journal of Pathology. 2006;169:2094-2103.) © 2006 American

Society for Investigative Pathology DOI: 10.2353/ajpath.2006.060191

Semen represents the main vector for human immunodeficiency virus

(HIV) dissemination worldwide and has been shown to harbor

replication-competent virus despite otherwise effective highly active

anti-retroviral therapy, which achieves undetectable viral load in

plasma. Despite this, the origin of seminal HIV particles remains

unclear, as does the question of whether the male genital tract

organs contribute virus to semen. Here we investigated the presence

of HIV receptors within the human testis using immunohistochemistry

and quantitative real-time polymerase chain reaction. We also

analyzed the infectivity of a dual tropic HIV-1 strain in an

organotypic culture, as well as the impact of viral exposure on

testosterone production.

Our study establishes that CXCR4+, CCR5+, CD4+, and DC-SIGN+ cells

are present within the interstitial tissue of human testis and that

these molecules persist throughout our organotypic culture. Our data

also reveal that the human testis is permissive to HIV-1 and supports

pro-ductive infection, leaving testosterone production apparently

unaffected. Infected cells appeared to be testicular macrophages

located within the interstitial tissue. That the testis itself

represents a potential source of virus in semen could play a role in

preventing viral eradication from semen because this organ

constitutes a pharmacological sanctuary for many current anti-

retrovirals.

http://news.bbc.co.uk/2/hi/health/6323191.stm