A type of immune cell that produces a glycoprotein called CD4 plays an important role in protecting mice infected with the Zika virus against severe neurological disease, according to a study published in the open-access journal PLOS Pathogensby Amelia Kahler Pinto of Saint Louis University, and colleagues.

Based on the findings, vaccines that induce strong responses from these immune cells, known as CD4+T cells, should be developed to prevent invasion of the Zika virus into the brain and spinal cord.

The Zika virus is a mosquito-borne virus that has recently spread throughout the Americas and the Caribbean. In some cases, Zika infection during pregnancy causes severe birth defects such as microencephaly–a condition in which a baby’s head is smaller than expected. Infection with the virus can also cause neurological disease in adults.

With growing awareness of the increased risk of severe neurological problems associated with Zika virus infection, focus has shifted toward detection, defining correlates of protection, and the development of a vaccine or antiviral to protect against disease progression. However, efforts focused on prevention and treatment have been limited by the lack of knowledge about how to generate a protective immune response against this emerging pathogen.

To address this gap in knowledge, Pinto and colleagues investigated the role of CD4+T cells in protecting against Zika virus disease affecting the nervous system using a mouse model of infection.

Mice lacking CD4+T cells showed more severe neurological symptoms such as limb paralysis and whole-body tremors, increased mortality, and significant increases in viral concentrations in the central nervous system (i.e., the brain and spinal cord). Moreover, the transfer of CD4+T cells from Zika-immunized mice protected susceptible mice from a potentially lethal dose of the virus.

The findings suggest that the CD4+T cell response is necessary and sufficient for control of Zika virus disease.

“The study reveals a novel role for CD4+T cells in providing protection against Zika virus infection and highlights the need for vaccines that elicit robust CD4+T cell responses to control viral replication within the central nervous system and prevent the exacerbation of severe neurological disease,” Pinto said.

How a virus destabilizes the genome

New insights into how Kaposi’s sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published September 13 in the open-access journal PLOS Pathogens by Erle Robertson of the University of Pennsylvania, and colleagues.
KSHV is associated with human malignancies and disorders marked by the excessive growth of white blood cells. KSHV-associated diseases are characterized by genetic alterations driven by chromosomal instability, as seen in numerous viral-associated cancer cells. It is still not entirely clear how viruses such as KSHV promote tumor growth. In the new study, Robertson and colleagues addressed this question by examining the molecular underpinnings of KSHV-induced chromosomal instability.

The findings reveal a novel mechanism by which a KSHV protein called LANA drives chromosomal instability. LANA directly induces aneuploidy–an abnormal number of chromosomes–and promotes cell proliferation. Specifically, this protein disrupts chromosome stability by inhibiting Bub1 phosphorylation of H2A and Cdc20, resulting in the dislocation of Shugoshin-1. Moreover, the NNLS domain of LANA plays key role in LANA-induced aneuploidy and cell proliferation. According to the authors, NNLS could be a promising target for the development of antiviral therapies for KSHV-associated cancers.

“Oncogenic viruses have developed strategies that are geared towards their survival,” the authors add. “Shugoshin-1 displacement is at the heart of viral genome survival and persistence in future generations of daughter cells.”

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