Humanized mice and HIV prevention

An estimated 33 million people are now infected with HIV worldwide. But a not so small reason why AIDS has slipped from the top of the news is the general agreement among experts that an effective HIV vaccine could be many more years in the making.

The situation has led some researchers to study alternative preventive strategies, including pre-exposure prophylaxis with antiretroviral drugs.

One scientist whose work in this area is of special importance is  J. Victor Garcia-Martinez, Ph.D., professor of medicine, division of infectious diseases at UNC, and a member of the university’s Institute for Global Health and Infectious Diseases.

A newcomer this year to the Carolina campus, Garcia-Martinez  carries  a broad pallette of research areas: humanized mice, retrovirology, AIDS, stem cell biology, and human gene therapy.

J. Victor Garcia-Martinez, Ph.D.

Humanized mice? Yes, since their inception less than 20 years ago, mice carrying transplanted, functional human tissue, genes, cells or organs have been used experimentally as in vivo human  stand-ins in biomedical research.

Today, we have a number of humanized mouse models with reconstituted immune systems.  And it may well be that the best of the bunch for HIV/AIDS research is the so-called humanized bone marrow-liver-thymus (BLT) mouse   developed by Garcia-Martinez .

With immune systems reconstituted from human bone marrow, liver and thymus transplants, BLT are the model mice that come with all the goods necessary in one package to simulate immune system functions of  Homo sap.

Here are a few reasons why: BLT mice could provide a model for prevention of intravaginal HIV infection. In one study, they have been shown to be susceptible to HIV transmission via a single intravaginal exposure.

Intravaginal exposure of these mice to HIV led to systemic HIV infection coupled with a rapid loss of human CD4+ T cells from the gastrointestinal mucosa, a known  hallmark of acute HIV infection in humans.

In this same  study, vaginal HIV infection was prevented in the BLT mice by pre-exposure prophylaxis using a combination of antiretroviral agents.

And in another study led by Garcia-Martinez, BLT mice were shown to be susceptible to HIV infection after a single intrarectal inoculation. This, too, coupled with loss of  CD4+ T cells from gut-associated lymphoid tissue and other evidence “closely mimics those observed in HIV infected humans.”

You might say these studies go beyond proof-of-concept to powerfully demonstrate why Garcia-Martinez’s mouse model holds promise for the preclinical evaluation of microbicides and antiretroviral prophylaxis regimens against HIV.

Click here for more details on the man and his work. And check this blog for reports of new research.

Les Lang


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