Henipavirus pathogenesis and antiviral approaches

Abstract

Hendra virus and Nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the Henipavirus genus. Both viruses induce generalized vasculitis affecting particularly the respiratory tract and CNS. The exceptionally broad species tropism of Henipavirus, the high case fatality rate and person-to-person transmission associated with Nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. Current therapeutic approaches, validated in animal models, target early steps in viral infection; they include the use of neutralizing virus-specific antibodies and blocking membrane fusion with peptides that bind the viral fusion protein. A better understanding of Henipavirus pathogenesis is critical for the further advancement of antiviral treatment, and we summarize here the recent progress in the field.

Keywords:

• bats
• emergent diseases
• encephalitis
• Hendra virus
• Nipah virus

Acknowledgments

We thank to F Jacquot, A Duthey, A Valve, L Barrot and other biosafety team members from INSERM BSL4 ‘Jean Mérieux’ for their assistance in animal experiment presented in the review and to P Lawrence (CIRI Lyon), for English editing.

Financial & competing interests disclosure

This work was supported by INSERM, ANR-09-MIEN-018-01, ANR-ASTRID-2011, ANR-13-PDOC-0010-01 (NITRODEP) and ECOFECT. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The high-case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options make Nipah virus a serious regional and potential global public health threat.

• Better understanding of the host–pathogen interaction in both the natural host, fruit bats, and in susceptible species is critical for further breakthroughs in the Henipavirus field.

• Virus may entry directly into CNS via olfactory nerves. In addition, the propagation of infection inside the host is highly facilitated by viral transmission via circulating leucocytes, which may, without being infected themselves, carry the virus and transfer the pathogen to the susceptible cells.

• Novel genetically and immunologically well-characterized small animal models should help new advances in the field.

• Interaction between Henipavirus nonstructural proteins and the host innate immune system may represent important targets for future drug development.

• Immunotherapy using passive antibody administration will rapidly provide the first available treatment.

• Observed efficiency of fusion inhibitory peptides offers exciting new therapeutic perspectives.

• Combination of several antiviral strategies may has the highest therapeutic potential.

• Additional studies may require a multidisciplinary approach, putting together virologists, immunologists, epidemiologists, veterinarians and physicians in the common endeavor of understanding and controlling Henipavirus infections.

Notes