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Double infection by HSV-2 and HIV: how does HSV-2 infection facilitate for HIV infection?

Objective

Globally, more than 40 million people are currently infected with HIV-1, with the vast majority of infections initiated at mucosal surfaces and approximately half of the world people now living with HIV are women. Herpes simplex type 2 (HSV-2) is one of the most common sexually transmitted viral diseases (STD) with an estimated prevalence of up to 50% among the female population worldwide giving rise to genital lesions and ulcers. Genital tract inflammation due to STD, such as HSV-2, increases expression of HIV receptors and co-receptors on all the resident target cells in genital mucosa. Apoptosis and apoptotic proteins, such as Fas have been showed to participate in homeostatic maintenance of vaginal epithelium. Considering the fact that disruption of the integrity of the vaginal mucosa resulting from HSV-2 heightens the risk of HIV transmission and may involve exacerbation of apoptosis mechanisms it is necessary to test how apoptosis during HSV-2 infection may add to disruption of vagina epithelium integrity and therefore, how it influences the outcome of double HIV-1/HSV-2 infection. To gain knowledge on this pathogenic scenario I will (i) identify the influence of HSV-2 on apoptosis and disruption of the vaginal mucosa using a mouse model of HSV-2 infection, (ii) examine the contribution of Fas and other receptors of the TNF family to vaginal epithelium lesions during HSV-2 infection (iii) analyze how HSV-2 infection can add to HIV-1 infection using double infection model of mice infected with HSV-2 and HIV-1/murine leukaemia A4070 pseudotype virus. Whenever applicable the relevance of the results obtained in the animal models will be verified in biopsy material from HSV-2 infected women. I expect that disclosure of the mechanisms responsible for increased susceptibility to HIV infection in HSV-2 infected women at the level of vaginal epithelial function will provide knowledge and opportunity to develop effective, affordable anti-HIV prophylactic therapy

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 232 646,60
Administrative Contact
Marlene Brink-Sinervo (Ms.)