Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2023 Aug 24:rs.3.rs-3210670.
doi: 10.21203/rs.3.rs-3210670/v1.

Alcohol Consumption Modifies Susceptibility to HIV-1 Entry in Cervical Mucosa-Derived CD4+ T cells of Women Resident in a Fishing Community of Lake Victoria, Uganda

Bagaya Bernard Ssentalo  1 , Emmanuella Driciru  1 , Muwanda Fahad  1 , Mary Nantongo  1 , Marion Namuleme  2 , Paul Kato Kitandwe  2 , Enoch Muyanja Ssekayita  2 , Ronald Galiwango  3 , Violet Mirembe  2 , Barbarah Kawoozo Muwenda  2 , Moses Muwanga  4 , Alex Kayongo  1 , Fredrick Lutwama  1
Affiliations

Alcohol Consumption Modifies Susceptibility to HIV-1 Entry in Cervical Mucosa-Derived CD4+ T cells of Women Resident in a Fishing Community of Lake Victoria, Uganda

Bagaya Bernard Ssentalo et al. Res Sq. .

Abstract

Background: A significant overlap exists in the burden of Alcohol Use Disorders (AUDs) and the HIV epidemic in Sub-Saharan Africa. Over 60% of HIV infections occur in women, mostly through the cervical mucosa. Absorption and systemic circulation of alcohol induces global physiological and immune effects, including at the genital mucosa. Alcohol alters expression of cell surface receptors, mucosal barrier permeability, inflammatory responses, and lymphocyte trafficking and homing. However, a substantial knowledge gap exists on whether these cellular and or immunological effects of alcohol modify the consumers' CD4+ T cell susceptibility to HIV-1 entry at the cervical mucosa. HIV seronegative women, aged 18-49 years were recruited from Kasenyi and Kigungu fish landing sites of Lake Victoria. They were categorized as Alcohol Consumers (n=27) or non-Alcohol Consumers (n=26) based on the World Health Organization Alcohol-Use-Disorder-Test (WHO-AUDIT) at a cut-off score of >=8/40 and <8/40, respectively. Cytobrush-collected Cervical Mononuclear Cells [CMCs] and Peripheral Blood Mononuclear Cells [PBMCs] from heparinized whole-blood were surface stained for CD4+ T cell immunophenotyping. To measure susceptibility to HIV entry, CMCs and PBMCs were co-cultured overnight with equal amount of GFP-tagged HIV-1 pseudo-virus particles. Both immunophenotyping and HIV entry were measured on a BD LSR II flow cytometer.

Results: There was no significant difference in the frequency of CD4+ T cells in blood (p=0.451) or mucosa (p=0.838) compartments across study groups. However, we observed a combined four-fold higher HIV entry (p=0.0001) into cervical versus blood-derived CD4+ T cells regardless of alcohol consumption status. More so, cervical-derived CD4+ T cells of alcohol-consumers showed a two-fold increase in susceptibility to HIV entry (P=0.0185) compared to the non-alcohol consumer group. Double positive α4β7+CD4+T cells of alcohol consumers exhibited a higher HIV entry compared to those from alcohol non-consumers(p=0.0069).

Conclusion: This study demonstrates that cervical CD4+ T cells are more susceptible to HIV entry than those from blood. Also, cervical CD4+ T cells of alcohol consumers are more susceptible than those of non-consumers. Differences in frequencies of α4β7+ CD4+ T between alcohol consumers and non-consumers' cells may account for the increased susceptibility to HIV entry.

Keywords: Alcohol Consumption; CD4+ T cells; Cervical mucosa; HIV-1; Susceptibility.

PubMed Disclaimer

Conflict of interest statement

Competing interests; The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Frequency of CD3+CD4+ T helper cells among alcohol consumers and their non-alcohol consumer counterparts. [A] Frequency in the Blood compartment, [B] Frequency in the cervical compartment
Figure 2
Figure 2
Frequency of GFP+CD4+T cells from the blood compartment compared to cervical mucosa compartment regardless of alcohol Use behaviour.
Figure 3
Figure 3
Frequency of GFP+ CD4+ T helper cells among alcohol consumers and their non-alcohol consumer counterparts. [A] Frequency in the Blood compartment, [B] Frequency in the cervical compartment
Figure 4
Figure 4
Frequency of integrin receptor chain expression by T helper cells in the cervical mucosa. [A] Frequency of α4+, [B] β7+ and [C] β1+ T helper cells
Figure 5
Figure 5
Frequency of GFP+ integrin receptor expressing cervical mucosa-derived T helper cells. [A] Frequency of GFP+α4β7+ T helper cells, and [B] Frequency of GFP+ α4β1+ T helper cells
See this image and copyright information in PMC

References

    1. (UPHIA), U.P.B.H.I.A., UGANDA POPULATION-BASED HIV IMPACT ASSESSMENT. Summary Sheet, 2017.
    1. Tanser F, d.O T., Maheu-Giroux M, Bärnighausen T., Concentrated HIV subepidemics in generalized epidemic settings. Curr Opin HIV AIDS., 2014. 9(2): p. 115–125. - PMC - PubMed
    1. Kwena Z.A., HIV in Fishing Communities: Prevalence, Incidence, Risk Factors, and Interventions. Conference on retroviruses and opportunistic infections, 2020(171).
    1. Anthony Kapesa N.B., Elias C.Nyanza, Mushi Martha F., Jahanpour Ola and Ngallaba Sospatro E., Prevalence of HIV infection and uptake of HIV/AIDS services among fisherfolk in landing Islands of Lake Victoria, north western Tanzania. BMC Health Services Research, 2018. 18(980): p. 1–9. - PMC - PubMed
    1. Lubega Muhamadi , N N., Nansubuga Sumaya, Hiire Edgar, Kigozi Godfrey, Nakigozi Gertrude, Lutalo Tom, Nalugoda Fred, Serwadda David, Gray Ronald, Wawer Maria, Kennedy Caitylin, Reynolds Steven James, Risk Denial and Socio-Economic Factors Related to High HIV Transmission in a Fishing Community in Rakai, Uganda: A Qualitative Study. PLOS ONE, 2015. 10(8): p. e0132740. - PMC - PubMed

Publication types