HIV1-Nef perturbs the integrity of blood testis barrier in rat model

ABSTRACT

The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

HIGHLIGHTS

• Established a rodent model to study the integrity of the blood testis barrier (BTB).

• Recombinant Nef (rNef) of HIV1 can breach the toughest physiological barrier of BTB.

• Integrity of BTB gets interrupted by rNef through the ‘disengagement’ and ‘engagement’ mechanisms of BTB dynamics.

• Major constituent proteins of BTB, including Occludin and ZO-1 were found to be highly disrupted by rNef; and seem to be the key aberrant for the compromised BTB.

• rNef also dislocated the localization of N & E cadherins in the rat testes; which would have affected the cadherin-based epithelial adhesion system of BTB and finally caused the breach.

KEYWORDS:

• Blood testis barrier
• HIV1Nef
• infertility blood testis barrier dynamics
• integrity
• permeability barrier
• tight junction
• viral protein
• ZO1

Acknowledgments

We are thankful for the support provided by The Director and National Laboratory Animal facility of CSIR- Central Drug Research Institute, Lucknow; the CDRI’s Communication number is 10795.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors contributions

Deependra Singh: Conceptualization, Data curation, Formal analysis, Methodology, Validation, Writing an original draft. Saurabh Kumar: Data curation, Formal analysis, Methodology, Review & editing of the original draft. Rajnikant Mishra: Data curation, Formal analysis, Methodology, Review & editing of the original draft. Anjali: Data curation, Formal analysis, Methodology, Review of the original draft. R. K. Tripathi: Conceptualization; Investigation; Supervision; Review & editing the original draft. Monika Sachdev: Conceptualization; Investigation; Supervision; Project administration; Resources; Validation; Visualization; Review & editing the original draft.

Data statements

Used data sets are available on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.