Background: One of the most benign (and thus successful) human pathogens is human herpes virus 7 (HHV-7), a T-cell tropic herpes virus. HHV-7 infects up to 70% of infants prior to the age of 2, and 95% of children have seroconverted by age 5 and often shed the virus asymptomatically via saliva. The absence of HHV-7-mediated pathology extends to immunosuppressed individuals, in sharp contrast to other members of the herpes virus family. Results of one study suggested that prior HHV-7 infection inhibited HIV-1 replication in some pediatric patients (pts). However, effects of HHV-7 upon HIV-1 replication and T-cell depletion are unknown. The ability of the virus to infect human cord blood cells, CD4⁺ T-cells, and the SUPT-1 thymocyte-like cell line suggested that HHV-7 would infect the thymus and secondary lymphoid organs. We hypothesized that HHV-7 infection could inhibit HIV replication and T-cell depletion in thymus and lymphoid explants.

Methods: Tissue explants were first infected with cell-free supernatant from mock infected or HHV-7 infected SUPT-1 cells. Cell-free HIV-1 supernatant from mock-, NL4- or HXB2-infected PBMC was used to infect the explants 24 h post-HHV-7 infection. Cells were harvested from the explants at various times post-infection (3–9 days). Surviving cells were counted by trypan blue exclusion and analyzed for virus replication by p24 ELISA (HIV) or Real Time PCR (HHV-7). Cells were analyzed for CD4, CD8, and CD3 expression by fluorescence activated cell sorter (FACS). The Student T-test method was employed for statistical analysis using Microsoft Excel software.

Results: Our results demonstrated that HHV-7 replicated in the explants, but did not significantly deplete cells compared to the mock-infected tissue. A slight decrease in the CD4/CD8 ratio during the culture period suggested that CD4 SP cells were being depleted in the HHV-7 tissue. However, unlike HIV-1 infection, there was no decrease in the relative percentage of CD4⁺CD8⁺ thymocytes associated with HHV-7 infection of the thymus. Surprisingly, the results suggested that HHV-7 co-infection enhanced HIV-1 replication (> 50-fold increase for NL4-3). In addition, co-infection of HHV-7 enhanced the replication of HXB2, an HIV-1 clone that does not normally replicate to detectable levels in the thymus.

Conclusions: HHV-7 infection of lymphoid explants did not significantly deplete T-cells, but co-infection with HHV-7 significantly enhanced HIV-1 replication.