Background:  Natural compounds in human body fluids or tissues may affect HIV infection and hence play a role in virus transmission or pathogenesis. However, it has frequently proven difficult to purify and characterize these agents because of the limited quantities of available human material and the lack of reliable methods.
Methods:  To overcome these limitations we have developed standardized methods to generate peptide libraries from body fluids or tissues.
 Screening of a comprehensive peptide library generated from human hemofiltrate led to the identification of a 20-residue peptide, designated VIRus-Inhibitory Peptide (VIRIP), which corresponds to a C-proximal region of α1-antitrypsin and inhibits HIV-1 by blocking the function of the gp41 fusion peptide. Interestingly, a few amino acid changes increased its antiretroviral potency by 2 orders of magnitude, making it interesting for clinical development. More recently, we screened a peptide library derived from seminal fluid to identify natural agents that might play a role in sexual transmission of HIV/AIDS.
Results:  We found that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) drastically enhance HIV infection. Further analyses showed that these peptides form amyloid-like fibrils, termed semen-derived enhancer of virus Infection (SEVI), that capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. In agreement with a relevant role in vivo we found that semen and seminal fluid also enhance HIV infection and provide evidence that fibril-forming PAP fragments contribute to this effect.
Conclusions:  Our ongoing experiments aim to further elucidate the enhancing mechanism and to identify agents that suppress this effect. Moreover, we are investigating the effect of seminal fluid and different fibrils on infection by other viruses to clarify whether amyloid-like aggregates may play a more general role in the spread of sexually transmitted diseases.