Evidence brief: Herpes simplex virus detection and genomes from under-sampled, remote populations

Abstract

Herpes simplex virus (HSV) is an endemic pathogen, infecting over half of all adults world-wide. HSV infection can cause a wide spectrum of disease outcomes, ranging from asymptomatic infection or mild lesions to rare cases of infectious keratitis, encephalitis, and death. HSV genome sequences differ between individuals and within individuals. To date, the vast majority of publicly available HSV genomic data has come from Europe and North America. Populations in South America, Africa, and Asia are under-sampled, as are non-industrial (e.g., agricultural, pastoral) populations, for which the natural environment plays a large role in health and disease dynamics. We used Whatman FTA card stabilization of DNA to develop a procedure for capturing oral and genital swabs from a geographically isolated pastoralist population in a desert region of northern Namibia. This is the first study to document HSV genome sequences from this type of remote setting and these are the first HSV genomes from Namibia. The resulting HSV sequences, collected in 2015 and 2016 from remote settlements in Namibia, fit within the scope of viral genetic diversity previously defined by African strains. The methodological approaches developed in this study can be expanded to broaden viral detection, improve diagnostics, and raise public health awareness about the burden of pathogens in under-served populations.

Introduction

Herpes simplex viruses (HSV) are large double-stranded DNA (dsDNA) viruses classified in the Alphaherpesvirinae sub-family of the Herpesviridae family [1]. There are two distantly related species, HSV-1 and HSV-2 (Simplexvirus humanalpha1 or 2), that infect human oral or genital niches. HSV-1 has established lifelong infections in about 67% of adults worldwide, or an estimated 3.7 billion people under the age of 50, while HSV-2 has infected an estimated 491 million [2]. While primary infection by HSV occurs at the mucosal epithelium, lifelong latency is established in the nervous system [1]. From this neuronal reservoir, the virus can reactivate in response to stressful stimuli. Reactivation enables the virus to return to the skin surface, initiate new shedding and/or lesions, and potentially transmit to new hosts.

Previous studies have shown that HSV isolates from unrelated individuals can differ between 2−4% in DNA identity genome-wide [3,4]. HSV-1 co-evolved with human ancestors while HSV-2 more recently crossed into humans and exhibits less diversity between human isolates [4–6]. Both HSV species have large dsDNA genomes of over 150 kb, which encode >75 proteins. This amount of variation can produce distinct coding differences in >60 proteins between any two unrelated isolates of HSV-1 [3,4,7]. HSV acquires genetic diversity by a variety of mechanisms, notably fluctuation in tandem repeat (TR) lengths, insertions/deletions (in/dels), single nucleotide polymorphisms (SNPs), and recombination events. Isolates with common geographic origins tend to group together in phylogenetic analyses, though these groupings show intermingling with the addition of recent isolates [3,4,6–15].