Abstract
While the global incidence of human immunodeficiency virus (HIV-1) remains well above UNAIDS targets, sexual transmission HIV is surprisingly inefficient. A variety of host, viral and environmental factors can either increase HIV-1 shedding in the infected partner and/or increase mucosal susceptibility of the HIV-1 uninfected partner. Clinical and epidemiological studies have clearly established that Neisseria gonorrhoeae substantially enhances HIV-1 transmission, despite it not being an ulcerative infection. This review will consider findings from molecular, immunologic and clinical studies that have focused on each of these two human-restricted pathogens, in order to develop an integrative model that describes how gonococci can both increase mucosal shedding of HIV-1 from a co-infected person and facilitate virus establishment in a susceptible host.
Highlights
It is remarkable to consider that human immunodeficiency virus type 1 (HIV-1) has caused a global pandemic despite being quite poorly transmissible, with the chance of an HIV-infected, treatment-naive individual passing the virus to their partner through penile-vaginal sex being a fraction of one percent (Royce et al, 1997; Galvin and Cohen, 2004)
The remainder of this review will bring these results together to develop an integrated model of how N. gonorrhoeae impacts HIV-1 shedding and susceptibility to HIV-1 infection, gaining insights from studies exploring the molecular and immunological processes that govern aspects of gonococcal infection with potential to impact upon HIV-1, as well as clinical studies exploring the impact of N. gonorrhoeae co-infection on an individual’s susceptibility to HIV-1 or their likelihood to transmit the virus to their partners
It is noteworthy that the gonococci unexpectedly elicit a potent plasmacytoid dendritic cells (pDCs) response, leading to a robust expression of interferon-α (IFNα), sufficient to cause a profound inhibition of HIV-1 replication in ex vivo cultures of peripheral blood cells from HIV-infected patients (DobsonBelaire et al, 2010). This effect is a consequence of the tendency of gonococci to liberate their genomic DNA, either by cellular lysis or their type 4 secretion system, which is detected by TLR9. This would seem to contradict the HIV1 stimulatory effect that has been ascribed to N. gonorrhoeae, pDCs are a double-edged sword with respect to HIV1 because the IFNα response can independently upregulate expression of viral-specific cellular defenses and recruit activated immune cells that can be infected by the virus (Martin-Moreno and Munoz-Fernandez, 2019)
Summary
It is remarkable to consider that human immunodeficiency virus type 1 (HIV-1) has caused a global pandemic despite being quite poorly transmissible, with the chance of an HIV-infected, treatment-naive individual passing the virus to their partner through penile-vaginal sex being a fraction of one percent (Royce et al, 1997; Galvin and Cohen, 2004) The explanation for this apparent contradiction is that multiple factors can enhance the likelihood of transmission, including the type of mucosa exposed to virus during sex, the viral titer in the anogenital secretions of the infected partner, and the presence/number of CD4 receptor-expressing target cells in the mucosa of the uninfected partner (Royce et al, 1997; Ferreira et al, 2014).
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