Significance of variation within HIV, EBV, and KSHV subtypes

Since their initial transmission to humans, viruses have diversified extensively through recombination and mutation. The presence of intra- and inter-individual viral diversity influences disease progression, drug resistance, and therapy and presumably explains the conflicting results in many studies, including the failure of peptide-based vaccination strategies. Although HIV is a small RNA virus, coinfection with large DNA viruses, notably the oncogenic gamma-herpesviridae human herpesvirus-8 and Epstein Barr virus, is common. This coinfection occurs secondary to immunosuppression and shared transmission routes with high-risk predisposing behavior. In addition, all 3 of these viruses can lead to chronic infections, long periods of latency, and reactivation characterized by pain and suffering. The efficient targeting of their genetic diversity represents one of the major challenges in their control, both in prophylactic and therapeutic strategies. An understanding of diversity will help delineate whether population-specific vaccine strategies are necessary.