Local replication of simian immunodeficiency virus in the breast milk compartment of chronically-infected, lactating rhesus monkeys

Abstract

Breast milk transmission remains a major mode of infant HIV acquisition, yet anatomic and immunologic forces shaping virus quasispecies in milk are not well characterized. In this study, phylogenic analysis of envelope sequences of milk SIV variants revealed groups of nearly identical viruses, indicating local virus production. However, comparison of the patterns and rates of CTL escape of blood and milk virus demonstrated only subtle differences between the compartments. These findings suggest that a substantial fraction of milk viruses are produced by locally-infected cells, but are shaped by cellular immune pressures similar to that in the blood.

Figure 1

Identification of groups of identical or nearly identical envelope sequences in breast milk of lactating, chronically SIV-infected rhesus monkeys. Trees were inferred by maximum likelihood methods [19]. Cell-associated and cell-free blood virus quasispecies env sequences are indicated with closed and open squares, respectively, and cell-associated and cell-free milk virus quasispecies env sequences are indicated with closed and open circles, respectively. Bayesian posterior probabilities are shown above the branch and bootstrap support values are shown in italics below the branch. Sequences are shown for three chronically infected rhesus macaques: 206 (week 74 after SIV infection), 402 (week 67 after SIV infection), and 403 (week 49 after SIV infection).