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Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture

Shen, C and Ding, M and Ratner, D and Montelaro, RC and Chen, Y and Gupta, P (2012) Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture. PLoS ONE, 7 (3).

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Background: Although there are different strains of HIV-1 in a chronically infected individual, only one or limited virus strains are successfully transmitted to a new individual. The reason for this "transmission bottleneck" is as yet unknown. Methodology/Principal Findings: A human cervical explant model was used to measure HIV-1 transmission efficiency of viral strains from chronic infections, and transmitter/founder variants. We also evaluated the genetic characteristics of HIV-1 variants in the inoculums compared to those transmitted across the cervical mucosa. Eight different HIV-1 isolates were used in this study, six chronic isolates and two transmitter/founder viruses. The transmission efficiency of the chronic and transmitter/founder virus isolates and the viral diversity of chronic isolates before and after viral transmission were assessed. The results indicate that transmitter/founder viruses did not display higher transmission efficiency than chronic HIV-1 isolates. Furthermore, no evidence for a difference in diversity was found between the inoculums and transmitted virus strains. Phylogenetic analysis indicated that the sequences of variants in the inoculums and those present in transmitted virus intermingled irrespective of co-receptor usage. In addition, the inoculum and transmitted variants had a similar pairwise distance distribution. Conclusion: There was no selection of a single or limited number of viral variants during HIV-1 transmission across the cervical mucosa in the organ culture model, indicating that the cervical mucosa alone may not produce the transmission bottleneck of HIV-1 infection observed in vivo. © 2012 Shen et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Shen, Cchs97@pitt.eduCHS97
Ding, Mmding@pitt.eduMDING
Ratner, Ddampf@pitt.eduDAMPF
Montelaro, RCrmont@pitt.eduRMONT
Chen, YCHENY@pitt.eduCHENY
Gupta, Ppgupta1@pitt.eduPGUPTA1
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 7 March 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 3
DOI or Unique Handle: 10.1371/journal.pone.0032539
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
MeSH Headings: Base Sequence; Cervix Uteri--immunology; Cervix Uteri--virology; Female; HIV Infections--immunology; HIV Infections--transmission; HIV-1--classification; HIV-1--genetics; HIV-1--immunology; Humans; Molecular Sequence Data; Mucous Membrane--immunology; Mucous Membrane--virology; Organ Culture Techniques; Phylogeny; env Gene Products, Human Immunodeficiency Virus--genetics
Other ID: NLM PMC3296723
PubMed Central ID: PMC3296723
PubMed ID: 22412886
Date Deposited: 13 Sep 2012 18:22
Last Modified: 02 Feb 2019 16:56


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