Table 3.

Studies on tissue explants to examine early stages of HIV-1 transmission.

STUDY	TISSUE SOURCE & METHODS	RESULTS & CONCLUSIONS
Patterson,2002 [7]	Tissue:   foreskins circumcised for phimosis, balanitis, adhesions and redundant foreskins               cervical tissue samples from removed uteri for benign conditions.Culture:  Three 4.0-mm biopsies from the IFS and three from the OFS cultured for 1 day.Infection:  Foreskins were infected with CCR5-using (R5) HIV-1Bal or the CXCR4-using (X4) HIV-1Lai for 1 day.Measuring of infectivity:  Infectivity quantified using real-time quantitative polymerase chain reaction for HIV-1 pol DNA.	Susceptibility of human foreskin to HIV-1:Infection was predominant in CD4 T cells and LCs of IFS.Infection was below the level of detection in OFS. Adult foreskin infection was higher than in an infant (22 months) foreskin.Adult foreskin from those without past history of STI’s was 9 times more susceptible than cervical tissue.
Fischetti L, 2009 [21]	Tissue :   Penile tissues( glans, urethra and foreskin tissues ) from gender reassignment patientsCulture:  Tissues sized 2-3 mm2 cultured for 10 days. Infection:  Cultured cells were exposed to HIV-1BaL or HIV-1Lai for 2 hours for infection. After resuspended in PHA medium overnight, the tissue explants were removed and cultured for 3 days.Measuring of infectivity: Assayed for HIV-1 P24 antigen level using ELISA from cultured supernatants harvested every 2-3 days.	Susceptibility of human foreskin to HIV-1:No significant differences in the level of HIV-1 infection between different tissue sites (glans, urethra, foreskin).No evidence to support enhanced susceptibility of IFS relative to OFS or glans. HIV-1 BaL productively infected all tissue sites, but no infection was detected with HIV-1 Lai.
Ganor Y, 2010 [22]	Tissue:  Normal healthy foreskin tissues circumcised due to personal reasons or phimosis.Culture: 8mm diameter round foreskin tissues used as novel ex-vivo explant model with restricted access of virus to the non-epidermal side of either IFS or OFS.Infection:    1. With low and high cell free HIV-1 loads.                    2. With PBMCs weakly or highly infected with HIV-1.Measuring infectivity:  Quantified HIV-1 by p24 ELISA.	Susceptibility of human foreskin to HIV-1:HIV-1 enters IFS explants, but is trapped within (thick) keratin layer of OFS. HIV-1 infected cells form viral synapses with apical keratinocytes.HIV-1 transmission is more effective when foreskin is inoculated with HIV infected cells, not the cell free virus.LC-T cell conjugates permit transfer of HIV-1 from LCs to T cells.Exposure of IFS to HIV-1 infected cells results in efficient translocation of HIV-1.Seminal plasma mixed with cervical-vaginal secretions decreases HIV-1 translocation through IFS.

IFS, inner foreskin; OFS, outer foreskin; LC, Langerhans cells STI, sexually transmitted infection.