Why HIV Virions Have Low Numbers of Envelope Spikes: Implications for Vaccine Development

The major structural proteins of most viruses, including both naked icosahedral and enveloped types, are present in a dense array on the virion surface. This pattern has likely evolved to promote structural integrity, maximize cell binding and entry, and minimize genome size. HIV and related simian lentiviruses are unusual in having a low density of envelope protein spikes on their surfaces (Figure 1) [1]. Why has HIV evolved this exceptional virion structure? We believe that studies of human papillomavirus (HPV) virus-like particles (VLPs), which are the basis of the highly successful HPV vaccine, may provide the conceptual underpinning for answering this question and key insights for developing effective HIV prophylactic vaccines. Figure 1 What's different about HIV virions? Why Does HIV Have So Few Virion Spikes? HIV is notably inefficient at transmission—it has been estimated that 200–2,000 encounters are required per heterosexual transmission event [2]. In large part this may be due to the low number (estimated to be 14, on average) of envelope spikes per virion, especially since increasing the number of envelope spikes per virion increases infectivity, at least in an in vitro simian immunodeficiency virus (SIV) model [1], [3]. It seems unlikely that HIV evolved a low number of envelope spikes to limit its transmission efficiency. Low density of env spikes may have evolved, in part, because it prevents bivalent binding of immunoglobulin G (IgG) antibodies to the virion, thus reducing antibody avidity and impeding neutralization [4]. However, we think that an alternative explanation for the selection for low numbers of envelope spikes is that this feature retards the induction of a broad spectrum antibody response.