Saliva and inhibition of HIV‐1 infection: molecular mechanisms

Shugars, Diane C.; Sweet, S. P.; Malamud, Daniel; Kazmi, Shamim H.; Page, Kimberly; Challacombe, Stephen

doi:10.1034/j.1601-0825.8.s2.7.x

Cited by 41 publications

(46 citation statements)

References 47 publications

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“…The panel of neutralizing antibodies used in this study represents both the previous generation of monoclonal antibodies (mAbs) with potent neutralization of subtype B HIV-1, yet importantly also includes more recently identified mAbs with extensive breadth even against the previously ''difficult to neutralize'' HIV-1 subtype C. The resistance profiles found for the infant clones described here are similar to other studies of newly infected infant viral variants of several HIV-1 subtypes. 14,16,36,41 While we saw little neutralization to 1b12 (Table 1) compared to some other studies where 50% or more of viruses were sensitive, 41,42 the results were similar to our previous study of uncultured Envelope pseudotypes from virus newly transmitted from mother to child. 15 Only one study of three infants infected through breast milk 39 also analyzed sensitivity to the recently identified broadly neutralizing PG9 and PG16 antibodies.…”

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confidence: 75%

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Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Russell

Ojeda

Fouda

et al. 2013

AIDS Research and Human Retroviruses

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Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, we address the question of whether specific viral characteristics are common to variants transmitted through breastfeeding that may facilitate evasion of innate or adaptive immune responses. We amplified the envelope gene (env) from the plasma of six infants during acute infection who were infected with HIV-1 subtype C through breastfeeding, and from three available matched maternal samples. We sequenced the full-length env genes in these subjects revealing heterogeneous viral populations in the mothers and homogeneous populations in the infants. In five infants, the viral population arose from a single variant, while two variants were detected in the remaining infant. Infant env sequences had fewer N-linked glycosylation sites and shorter sequences than those of the available matched maternal samples. Though the small size of the study precluded our ability to test statistical significance, these results are consistent with selection for virus with shorter variable loops and fewer glycosylation sites during transmission of HIV-1 subtype C in other settings. Transmitted envs were resistant to neutralization by antibodies 2G12 and 2F5, but were generally sensitive to the more broadly neutralizing PG9, PG16, and VRC01, indicating that this new generation of broadly neutralizing monoclonal antibodies could be efficacious in passive immunization strategies.T ransmission of human immunodeficiency virus-1 (HIV-1) through breastfeeding (BF) makes up one-third to one-half of all mother-to-child transmission events.1 The mechanism(s) of transmission, however, are poorly understood. The oral cavity and gastrointestinal tract of breastfed infants are exposed daily to both cell-free and cell-associated HIV-1, 2-4 yet the majority of infants remain uninfected even if neither mother nor baby receive antiretroviral prophylaxis. 5This inefficiency of transmission indicates that anatomical, innate, and/or adaptive mechanisms of protection are able to prevent transmission to a great extent.6-11 Maternal antibodies could prevent infection either through direct binding of virus in the breast milk, or by their systemic and mucosal presence in the infant. This passive maternal immunity in the infant increases in concentration during the last trimester of gestation, and continues to pass into the infant through breastfeeding.Studies of in utero and intrapartum transmission have shown a universal bottleneck in genetic diversity from mother to child, as well as differences in the characteristics of transmitted virus for in utero versus intrapartum transmission. 12,13 Data are very limited for breastfeeding pairs, but one study of three breast milk transmission events found a similar bottleneck for HIV-1 subtype A.14 We previously demonstrated that the viral population found in ...

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supporting

confidence: 75%

“…These antibodies clearly have enhanced breadth that includes neutralization of subtype C, and for this reason may represent a useful tool for passive immunization in regions where clade C HIV-1 is prevalent. 41 These data in particular support the CD4 binding site as a promising target for infant vaccine design.…”

mentioning

confidence: 83%

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Russell

Ojeda

Fouda

et al. 2013

AIDS Research and Human Retroviruses

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“…Endogenous anti-HIV-1 activity has been demonstrated in whole, parotid, and submandibular/sublingual (sm/sl) saliva, colostrum, whole milk, and seminal plasma (1,11,13,24,29,32,38,45,46,51) but not in cerebrospinal fluid or urine (38). The incidence of oral HIV-1 transmission is very low and can be attributed both to endogenous salivary factors that prevent oral excretion of transmissible levels of virus (45,47,48) and to lysis of HIV-infected cells due to the hypotonicity of saliva (2,3).…”

mentioning

confidence: 99%

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

Kazmi

Naglik

Sweet

et al. 2006

Clin Vaccine Immunol

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Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

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“…It has been well described for the past decade or more that a variety of salivary inhibitors decrease HIV-1 infectivity in the oral cavity (108,109). Nonetheless, ongoing studies have suggested that oral transmission of the virus remains quite common in a number of important settings in vivo (6,7,51).…”

mentioning

confidence: 99%

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Acheampong¹,

Parveen²,

Muthoga³

et al. 2005

J Virol

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Saliva and inhibition of HIV‐1 infection: molecular mechanisms

Cited by 41 publications

References 47 publications

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

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